/opt/conda/conda-bld/coot-headless_1759975870518/work/api/coot-molecule.hh

/*
 * api/coot-molecule.hh
 *
 * Copyright 2020 by Medical Research Council
 * Author: Paul Emsley
 *
 * This file is part of Coot
 *
 * This program is free software; you can redistribute it and/or modify
 * it under the terms of the GNU Lesser General Public License as published
 * by the Free Software Foundation; either version 3 of the License, or (at
 * your option) any later version.
 *
 * This program is distributed in the hope that it will be useful, but
 * WITHOUT ANY WARRANTY; without even the implied warranty of
 * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the GNU
 * General Public License for more details.
 *
 * You should have received a copies of the GNU General Public License and
 * the GNU Lesser General Public License along with this program; if not,
 * write to the Free Software Foundation, Inc., 51 Franklin Street,
 * Fifth Floor, Boston, MA, 02110-1301, USA.
 * See http://www.gnu.org/licenses/
 *
 */
 
#ifndef COOT_MOLECULE_HH
#define COOT_MOLECULE_HH
 
#include <utility>
#include <atomic>
#include <array>
#include <set>
 
 
#include "compat/coot-sysdep.h"
 
#include <clipper/core/xmap.h>
#include "utils/ctpl.h"
#include "utils/coot-fasta.hh"
#include "coot-utils/atom-selection-container.hh"
#include "coot-utils/coot-rama.hh"
#include "coot-utils/sfcalc-genmap.hh"
#include "coot-utils/atom-tree.hh"
#include "coot-utils/texture-as-floats.hh"
#include "coot-utils/coot-align.hh"
#include "geometry/residue-and-atom-specs.hh"
#include "coords/Cartesian.hh"
#include "coords/Bond_lines.hh"
#include "ideal/simple-restraint.hh"
#include "ideal/extra-restraints.hh"
#include "coot-utils/simple-mesh.hh"
#include "ghost-molecule-display.hh"
 
#ifdef MAKE_ENHANCED_LIGAND_TOOLS
#include "lidia-core/rdkit-interface.hh"
#endif
 
#include "density-contour/CIsoSurface.h"
#include "gensurf.hh"
#include "coot-utils/coot-shelx.hh"
 
#include "coot-colour.hh" // put this in utils
 
#include "coords/mmdb-extras.hh"
#include "merge-molecule-results-info-t.hh"
#include "phi-psi-prob.hh"
 
#include "coot-utils/atom-overlaps.hh"
#include "symmetry-info.hh" // contains cell
 
#include "instancing.hh"
 
#include "generic-3d-lines.hh"
 
#include "coot-simple-molecule.hh"
 
#include "coot-utils/coot-map-utils.hh" // for map_molecule_centre_info_t
#include "api-cell.hh" // 20230702-PE not needed in this file - remove it from here
 
#include "moved-atom.hh"
#include "moved-residue.hh"
 
#include "bond-colour.hh"
#include "blender-mesh.hh"
#include "user-defined-colour-table.hh"
 
// 2023-07-04-PE This is a hack. This should be configured - and the
// various functions that depend on this being true should be
// reworked so that they run without a thread pool.
 
#ifdef HAVE_BOOST_THREAD // part of DEFS in Makefile
#define HAVE_BOOST_BASED_THREAD_POOL_LIBRARY
#endif
 
#include "plain-atom-overlap.hh"
 
 
namespace coot {
 
   enum { RESIDUE_NUMBER_UNSET = -1111}; // from molecule-class-info
 
   class residue_range_t {
   public:
      residue_range_t() : res_no_start(-999), res_no_end(-999) {}
      residue_range_t(const std::string &c, int r1, int r2) : res_no_start(r1), res_no_end(r2) {}
      std::string chain_id;
      int res_no_start;
      int res_no_end;
   };
 
   class atom_distance_t {
   public:
     atom_distance_t(const atom_spec_t &a1, const atom_spec_t &a2,
            float d) : atom_1(a1), atom_2(a2), distance(d) {}
     atom_distance_t() : distance(-1) {}
     atom_spec_t atom_1;
     atom_spec_t atom_2;
     float distance;
   };
 
   class molecule_t {
 
      class molecule_save_info_t {
      public:
         // ints because we subtract from them.
         std::pair<time_t, int> last_saved;
         int modification_index;
         int max_modification_index;
         molecule_save_info_t() : last_saved(std::make_pair(0,0)), modification_index(0),
                                  max_modification_index(0) {}
         void new_modification(const std::string &mod_string) {
            modification_index++;
            if (false) // debugging
               std::cout << "new_modification: moved on to " << modification_index
                         << " by " << mod_string << std::endl;
            if (modification_index > max_modification_index)
               max_modification_index = modification_index;
         }
         void made_a_save() {
            // this is called when the server says that it has saved the file
            last_saved.first = time(nullptr);
            last_saved.second = modification_index;
         }
         bool have_unsaved_changes() const {
            return modification_index > last_saved.second;
         }
         std::string index_string(int idx) const {
            return std::to_string(idx);
         }
         void set_modification_index(int idx) {
            // undo() and redo() (acutally restore_from_backup()) use this.
            // the index is the idx number given to restore_from_backup() by
            // the functions below
            modification_index = idx;
         }
         int get_previous_modification_index() const {
            return modification_index - 1;
         }
         int get_next_modification_index() const {
            return modification_index + 1;
         }
      };
 
      // molecule_save_info_t save_info;
 
 
      class modification_info_t {
      public:
         class save_info_t {
         public:
            save_info_t(const std::string &file_name, const std::string &mis) : file_name(file_name), modification_info_string(mis) {}
            std::string file_name;
            std::string modification_info_string;
            mmdb::Manager *get_mol();
         };
      private:
         void init() {};
         void print_save_info() const;
      public:
         modification_info_t() : backup_dir("coot-backup"), mol_name("placeholder"), is_mmcif_flag(false),
                                 modification_index(0), max_modification_index(0) {}
         modification_info_t(const std::string &mol_name_for_backup, bool is_mmcif) :
            backup_dir("coot-backup"), mol_name(mol_name_for_backup), is_mmcif_flag(is_mmcif),
            modification_index(0), max_modification_index(0) {}
         std::string backup_dir;
         std::string mol_name; // used in construction of filename, it is a stub to which we add an extension
         bool is_mmcif_flag;
         std::vector<save_info_t> save_info;
         int modification_index;
         int max_modification_index;
         bool have_unsaved_changes() const;
         void set_molecule_name(const std::string &molecule_name, bool is_mmcif) { mol_name = molecule_name; is_mmcif_flag = is_mmcif; }
         std::string get_index_string(int idx) const { return std::to_string(idx); }
         std::string get_backup_file_name_from_index(int idx) const;
         std::string make_backup(mmdb::Manager *mol, const std::string &modification_info_string);
         mmdb::Manager *undo(mmdb::Manager *mol);
         mmdb::Manager *redo();
 
      };
 
      modification_info_t modification_info;
 
      bool use_gemmi; // true now
      int imol_no; // this molecule's index in the container vector
      bool is_closed_flag;
      int ligand_flip_number;
      std::string name;
      bool is_from_shelx_ins_flag;
      ShelxIns shelxins;
 
      std::map<residue_spec_t, int> current_rotamer_map;
      bool really_do_backups; // default true
 
      // private
      void makebonds(protein_geometry *geom, rotamer_probability_tables *rotamer_tables_p,
                     const std::set<int> &no_bonds_to_these_atoms,
                     bool draw_hydrogen_atoms_flag, bool draw_missing_loops_flag);
 
#if defined __has_builtin
#if __has_builtin (__builtin_FUNCTION)
      void make_bonds_type_checked(protein_geometry *geom, rotamer_probability_tables *rot_prob_tables_p, bool draw_hydrogen_atoms_flag, bool draw_missing_loops_flag, const char *s = __builtin_FUNCTION());
      void make_bonds_type_checked(protein_geometry *geom, const std::set<int> &no_bonds_to_these_atom_indices, bool draw_hydrogen_atoms_flag, bool draw_missing_loops_flag, const char *s = __builtin_FUNCTION());
#else
      void make_bonds_type_checked(protein_geometry *geom, const char *s = 0);
      void make_bonds_type_checked(protein_geometry *geom, rotamer_probability_tables *rot_prob_tables_p, bool draw_hydrogen_atoms_flag, bool draw_missing_loops_flag, const char *s = 0);
#endif
#else // repeat above
      void make_bonds_type_checked(protein_geometry *geom, const char *s = 0);
      void make_bonds_type_checked(protein_geometry *geom, rotamer_probability_tables *rot_prob_tables_p, bool draw_hydrogen_atoms_flag, bool draw_missing_loops_flag, const char *s = 0);
#endif
 
      api_bond_colour_t bonds_box_type; // public accessable via get_bonds_box_type(); // wass Bonds_box_type()
      graphical_bonds_container bonds_box;
      api_bond_colour_t get_bonds_box_type() const { return bonds_box_type; }
 
      // this is the bond dictionary also mode.
      // 20221011-PE force_rebonding arg is not currently used.
      void make_colour_by_chain_bonds(protein_geometry *geom,
                                      const std::set<int> &no_bonds_to_these_atoms,
                                      bool change_c_only_flag,
                                      bool goodsell_mode,
                                      bool draw_hydrogen_atoms_flag,
                                      bool draw_missing_loops_flag,
                                      bool do_rota_markup=false,
                                      rotamer_probability_tables *rotamer_tables_p = nullptr,
                                      bool force_rebonding=true);
      void make_ca_bonds();
      // just a copy of the version in src
      float bonds_colour_map_rotation;
      // std::vector<glm::vec4> make_colour_table(bool against_a_dark_background) const; public now
      glm::vec4 get_bond_colour_by_colour_wheel_position(int icol, api_bond_colour_t bonds_box_type) const;
      colour_t get_bond_colour_by_mol_no(int colour_index, bool against_a_dark_background) const;
      colour_t get_bond_colour_basic(int colour_index, bool against_a_dark_background) const;
      bool use_bespoke_grey_colour_for_carbon_atoms;
      colour_t bespoke_carbon_atoms_colour;
 
      void update_map_triangles(float radius, Cartesian centre, float contour_level); // using vector of threads
      void update_map_triangles_using_thread_pool(float radius, Cartesian centre, float contour_level, ctpl::thread_pool *thread_pool_p);
 
      short int is_em_map_cached_flag; // -1 mean unset (so set it, 0 means no, 1 means yes)
      short int is_em_map_cached_state(); // set is_em_map_cached_flag if not set
      ghost_molecule_display_t map_ghost_info;
 
      bool xmap_is_diff_map;
      bool has_xmap() const { return is_valid_map_molecule(); }
 
      colour_holder map_colour;
      glm::vec4 position_to_colour_using_other_map(const clipper::Coord_orth &position,
                                                   const clipper::Xmap<float> &other_map_for_colouring) const;
      float other_map_for_colouring_min_value;
      float other_map_for_colouring_max_value;
      glm::vec4 fraction_to_colour(float f) const; // for other map colouring - perhaps this function name is too generic?
      bool  radial_map_colour_invert_flag;
      float radial_map_colour_saturation;
 
      // save the data used for the fourier, so that we can use it to
      // sharpen the map:
      // uncommenting the following line causes a crash in the multi-molecule
      // (expand molecule space) test.
      bool original_fphis_filled;
      bool original_fobs_sigfobs_filled;
      bool original_fobs_sigfobs_fill_tried_and_failed;
      clipper::HKL_data< clipper::datatypes::F_phi<float> >  *original_fphis_p;
      clipper::HKL_data< clipper::datatypes::F_sigF<float> > *original_fobs_sigfobs_p;
      clipper::HKL_data< clipper::data32::Flag> *original_r_free_flags_p;
 
      void clear_draw_vecs();
      void clear_diff_map_draw_vecs();
      std::vector<density_contour_triangles_container_t> draw_vector_sets;
      std::vector<density_contour_triangles_container_t> draw_diff_map_vector_sets;
      std::vector<std::pair<int, TRIANGLE> > map_triangle_centres; // with associated mid-points and indices
 
      // insert coords - c.f function in molecule-class-info_t
      void insert_coords_internal(const atom_selection_container_t &asc);
 
      // This function no longer does a backup or updates the save_info!
      // The calling function should do that.
      void replace_coords(const atom_selection_container_t &asc,
                          bool change_altconf_occs_flag,
                          bool replace_coords_with_zero_occ_flag);
      // helper function for above function
      bool movable_atom(mmdb::Atom *mol_atom, bool replace_coords_with_zero_occ_flag) const;
      bool moving_atom_matches(mmdb::Atom *at, int this_mol_index_maybe) const;
      void adjust_occupancy_other_residue_atoms(mmdb::Atom *at,
                                                mmdb::Residue *residue,
                                                short int force_sum_1_flag);
 
      // return -1 on failure
      int full_atom_spec_to_atom_index(const atom_spec_t &atom_spec) const;
      // return -1 on no atom found.
      int full_atom_spec_to_atom_index(const std::string &chain,
                                       int resno,
                                       const std::string &insertion_code,
                                       const std::string &atom_name,
                                       const std::string &alt_conf) const;
 
      std::string name_for_display_manager() const;
      std::string dotted_chopped_name() const;
      // std::string get_save_molecule_filename(const std::string &dir);
      std::string make_backup(const std::string &modification_type); // returns warning message, otherwise empty string
      void save_history_file_name(const std::string &file);
      std::vector<std::string> history_filename_vec;
      std::string save_time_string;
      void restore_from_backup(int mod_index, const std::string &cwd);
 
      std::vector<atom_spec_t> fixed_atom_specs;
 
      std::pair<int, mmdb::Residue *>
      find_serial_number_for_insert(int seqnum_for_new,
                                    const std::string &ins_code_for_new,
                                    const std::string &chain_id) const;
 
      // remove TER record from residue
      //
      void remove_TER_internal(mmdb::Residue *res_p);
      void remove_TER_on_last_residue(mmdb::Chain *chain_p);
      std::pair<bool, std::string> unused_chain_id() const;
      int append_to_molecule(const minimol::molecule &water_mol);
 
      glm::vec4 colour_holder_to_glm(const colour_holder &ch) const;
 
      std::pair<bool, Cartesian> get_HA_unit_vector(mmdb::Residue *r) const;

      void setup_cylinder_clashes(instanced_mesh_t &im, const atom_overlaps_dots_container_t &c,
                                  float ball_size, unsigned int num_subdivisions,
                                  const std::string &molecule_name_stub) const;

      void setup_dots(instanced_mesh_t &im,
                      const atom_overlaps_dots_container_t &c,
                      float ball_size, unsigned int num_subdivisions,
                      const std::string &molecule_name_stub) const;
 
      // ====================== SHELX stuff ======================================
 
      std::pair<int, std::string> write_shelx_ins_file(const std::string &filename) const;
      int read_shelx_ins_file(const std::string &filename);
      // return the success status, 0 for fail, 1 for good.
      int add_shelx_string_to_molecule(const std::string &str);
      bool is_from_shelx_ins() const { return is_from_shelx_ins_flag; }
 
      void trim_atom_label_table();
      void delete_ghost_selections();
      void update_symmetry();
      bool show_symmetry;

      void delete_any_link_containing_residue(const residue_spec_t &res_spec);
      // this doesn't do a backup - the calling function is in charge of that
      void delete_link(mmdb::Link *link, mmdb::Model *model_p);
 
      bool sanity_check_atoms(mmdb::Manager *mol) const; // sfcalc_genmap crashes after merge of ligand.
      // Why? Something wrong with the atoms after merge?
      // Let's diagnose.... Return false on non-sane.
 
      // internal function for public rotamer functions
      int set_residue_to_rotamer_move_atoms(mmdb::Residue *res, mmdb::Residue *moving_res);
 
      // ====================== Jiggle-Fit (internal) ================================
 
      float fit_to_map_by_random_jiggle(mmdb::PPAtom atom_selection,
                                        int n_atoms,
                                        const clipper::Xmap<float> &xmap,
                                        float map_sigma,
                                        int n_trials,
                                        float jiggle_scale_factor,
                                        bool use_biased_density_scoring,
                                        std::vector<mmdb::Chain *> chains_for_moving);
 
      minimol::molecule rigid_body_fit(const minimol::molecule &mol_in,
                                             const clipper::Xmap<float> &xmap,
                                             float map_sigma) const;
 
      // ====================== validation ======================================
 
      std::vector<coot::geometry_distortion_info_container_t>
      geometric_distortions_from_mol(const atom_selection_container_t &asc, bool with_nbcs,
                                     coot::protein_geometry &geom,
                                     ctpl::thread_pool &static_thread_pool);
 
 
      // ====================== dragged refinement ======================================
 
      coot::restraints_container_t *last_restraints;
 
      // ====================== init ======================================
 
      void init() {
         is_closed_flag = false; // changed on close_yourself()
         // use_gemmi = true; // 20240112-PE  woohoo! Let the bugs flow!
         // 20240118 Turns out the bugs flowed too much. Let's set this back to false.
         use_gemmi = false;
         // set the imol before calling this function.
         ligand_flip_number = 0;
         bonds_box_type = api_bond_colour_t::UNSET_TYPE;
         is_em_map_cached_flag = false;
         xmap_is_diff_map = false;
         is_from_shelx_ins_flag = false;
         show_symmetry = false;
         default_temperature_factor_for_new_atoms = 20.0;
         original_fphis_filled = false;
         original_fobs_sigfobs_filled = false;
         original_fobs_sigfobs_fill_tried_and_failed = false;
         original_fphis_p = nullptr;
         original_fobs_sigfobs_p = nullptr;
         original_r_free_flags_p = nullptr;
         refmac_r_free_flag_sensible = false;
         use_bespoke_grey_colour_for_carbon_atoms = false;
         really_do_backups = true;
 
         radial_map_colour_saturation = 0.5;
         radial_map_colour_invert_flag = false;
 
         other_map_for_colouring_min_value = 0.0;
         other_map_for_colouring_max_value = 1.0;
 
         map_colour = colour_holder(0.3, 0.3, 0.7);
         last_restraints = nullptr;
 
         float rotate_colour_map_on_read_pdb = 0.24;
         bonds_colour_map_rotation = (imol_no + 1) * rotate_colour_map_on_read_pdb;
         while (bonds_colour_map_rotation > 360.0)
            bonds_colour_map_rotation -= 360.0;
 
         base_colour_for_bonds = colour_holder(0.43, 0.33, 0.2);
 
         fill_default_colour_rules();
         if (false) {
            auto v = get_colour_rules();
            std::cout << "colour rules: " << std::endl;
            std::cout << "-------------" << std::endl;
            for (unsigned int i=0; i<v.size(); i++) {
               std::cout << i << " " << v[i].first << " " << v[i].second << std::endl;
            }
            std::cout << "-------------" << std::endl;
         }
 
         indexed_user_defined_colour_selection_cids_apply_to_non_carbon_atoms_also = true;
 
         gltf_pbr_roughness = 0.2;
         gltf_pbr_metalicity = 0.0;
 
      }
 
      // chain-id (maybe) and plain sequence.
      coot::fasta_multi multi_fasta_seq;
 
      static std::string file_to_string(const std::string &fn);
 
   public:
 
      // ---------------------------------------------------------------------------------------------------------------
      // ---------------------------------------------------------------------------------------------------------------
      //                                 public
      // ---------------------------------------------------------------------------------------------------------------
      // ---------------------------------------------------------------------------------------------------------------
 
      // enum refine_residues_mode {SINGLE, TRIPLE, QUINTUPLE, HEPTUPLE, SPHERE, BIG_SPHERE, CHAIN, ALL};
 
      atom_selection_container_t atom_sel;
      // set this on reading a pdb file
      float default_temperature_factor_for_new_atoms; // direct access
 
      // for rsr neighbours - they are fixed.
      std::vector<std::pair<bool, mmdb::Residue *> > neighbouring_residues;

      molecule_t(const std::string &name_in, int mol_no_in) : name(name_in) {imol_no = mol_no_in; init(); }
      molecule_t(const std::string &name_in, int mol_no_in, short int is_em_map) : name(name_in) {
         imol_no = mol_no_in; init(); is_em_map_cached_flag = is_em_map; }

      molecule_t(const std::string &name_in, int mol_no_in, const clipper::Xmap<float> &xmap_in, bool is_em_map_flag)
         : name(name_in), xmap(xmap_in) {imol_no = mol_no_in; init(); is_em_map_cached_flag = is_em_map_flag; }

      explicit molecule_t(atom_selection_container_t asc, int imol_no_in, const std::string &name_in) : name(name_in), atom_sel(asc) {
         imol_no = imol_no_in;
         init();
         default_temperature_factor_for_new_atoms =
            util::median_temperature_factor(atom_sel.atom_selection,
                                            atom_sel.n_selected_atoms,
                                            99999.9, 0.0, false, false);
      }
 
      float get_median_temperature_factor() const;
 
      float get_temperature_factor_of_atom(const std::string &atom_cid) const;
 
      // ------------------------ close
 
      int close_yourself();
 
      bool is_closed() const { return is_closed_flag; }
 
      // --------------------- backups
 
      void set_really_do_backups(bool state) { really_do_backups = state; }
 
      // ------------------------------- rsr utils
      // - add in the environment of this fragment molecule
      // from the residue from which this fragment was copied
      void add_neighbor_residues_for_refinement_help(mmdb::Manager *mol);
 
      // ----------------------- structure factor stuff ------------------------------------------------------
 
      void fill_fobs_sigfobs(); // re-reads MTZ file (currently 20210816-PE)
 
      // used to be a const ref. Now return the whole thing!. Caller must call
      // fill_fobs_sigfobs() directly before using this function - meh, not a good API.
      // Return a *pointer* to the data so that we don't get this hideous non-reproducable
      // crash when we access this data item after the moelcule vector has been resized
      // 20210816-PE.
      // CAUTION: this function can throw a std::runtime_error.
      clipper::HKL_data<clipper::data32::F_sigF> *get_original_fobs_sigfobs() const {
         if (!original_fobs_sigfobs_filled) {
            std::string m("Original Fobs/sigFobs is not filled");
            throw(std::runtime_error(m));
         }
         return original_fobs_sigfobs_p;
      }
 
      clipper::HKL_data<clipper::data32::Flag> *get_original_rfree_flags() const {
         if (!original_fobs_sigfobs_filled) {
            std::string m("Original Fobs/sigFobs is not filled - so no RFree flags");
            throw(std::runtime_error(m));
         }
         return original_r_free_flags_p;
      }
      // use this molecules mol and the passed data to make a map for some other
      // molecule
      int sfcalc_genmap(const clipper::HKL_data<clipper::data32::F_sigF> &fobs,
                        const clipper::HKL_data<clipper::data32::Flag> &free,
                        clipper::Xmap<float> *xmap_p);
      util::sfcalc_genmap_stats_t
      sfcalc_genmaps_using_bulk_solvent(const clipper::HKL_data<clipper::data32::F_sigF> &fobs,
                                        const clipper::HKL_data<clipper::data32::Flag> &free,
                                        clipper::Xmap<float> *xmap_2fofc_p,
                                        clipper::Xmap<float> *xmap_fofc_p);
      // String munging helper function (for reading mtz files).
      // Return a pair.first string of length 0 on error to construct dataname(s).
      std::pair<std::string, std::string> make_import_datanames(const std::string &fcol,
                                                                const std::string &phi_col,
                                                                const std::string &weight_col,
                                                                int use_weights) const;
      // make these private?
      std::string refmac_fobs_col;
      std::string refmac_sigfobs_col;
      std::string refmac_mtz_filename;
      std::string refmac_r_free_col;
      std::string Refmac_fobs_col() const { return refmac_fobs_col; }
      std::string Refmac_sigfobs_col() const { return refmac_sigfobs_col; }
      std::string Refmac_mtz_filename() const { return refmac_mtz_filename; }
      bool refmac_r_free_flag_sensible;
 
      void associate_data_mtz_file_with_map(const std::string &data_mtz_file_name,
                                            const std::string &f_col, const std::string &sigf_col,
                                            const std::string &r_free_col);
 
      // ----------------------- xmap
 
      clipper::Xmap<float> xmap; // public because the filling function needs access
 
      // public access to the lock (from threads)
      static std::atomic<bool> draw_vector_sets_lock;
 
      util::map_molecule_centre_info_t get_map_molecule_centre() const;
 
      // ----------------------- utils
 
      void replace_molecule_by_model_from_file(const std::string &pdb_file_name);
 
      std::string get_name() const { return name; }
      void set_molecule_name(const std::string &n) { name = n; };
      int get_molecule_index() const { return imol_no; }
      // void set_molecule_index(int idx) { imol_no = idx; } // 20221011-PE needed?
      bool is_valid_model_molecule() const;
      bool is_valid_map_molecule() const;
      unsigned int get_number_of_atoms() const;
      int get_number_of_hydrogen_atoms() const;
      float get_molecule_diameter() const;
      double get_radius_of_gyration() const;

      std::vector<std::string> get_types_in_molecule() const;
      mmdb::Residue *cid_to_residue(const std::string &cid) const;
      std::vector<mmdb::Residue *> cid_to_residues(const std::string &cid) const;
      mmdb::Atom *cid_to_atom(const std::string &cid) const;
      std::pair<bool, residue_spec_t> cid_to_residue_spec(const std::string &cid) const;
      std::pair<bool, atom_spec_t> cid_to_atom_spec(const std::string &cid) const;
      std::vector<std::string> get_residue_names_with_no_dictionary(const protein_geometry &geom) const;
      // here res-name might be HOH or DUM
      int insert_waters_into_molecule(const minimol::molecule &water_mol, const std::string &res_name);
 
      // ----------------------- model utils

     std::vector<residue_range_t> get_missing_residue_ranges() const;
 
      // public
      void make_bonds(protein_geometry *geom, rotamer_probability_tables *rot_prob_tables_p,
                      bool draw_hydrogen_atoms_flag, bool draw_missing_loops_flag);

      std::vector<glm::vec4> make_colour_table(bool against_a_dark_background) const;
      std::vector<glm::vec4> make_colour_table_for_goodsell_style(float colour_wheel_rotation_step,
                                                                  float saturation, float goodselliness) const;
 
      // for debugging
      void print_colour_table(const std::string &debugging_label) const;
 
      // print_secondary_structure_info
      void print_secondary_structure_info() const;
 
      // returns either the specified atom or null if not found
      mmdb::Atom *get_atom(const atom_spec_t &atom_spec) const;
      // returns either the specified residue or null if not found
      mmdb::Residue *get_residue(const residue_spec_t &residue_spec) const;
 
      // can return null
      mmdb::Residue *get_residue(const std::string &residue_cid) const;
 
      std::string get_residue_name(const residue_spec_t &residue_spec) const;
 
      bool have_unsaved_changes() const { return modification_info.have_unsaved_changes(); }
      int undo(); // 20221018-PE return status not yet useful
      int redo(); // likewise
      // the return value of WritePDBASCII() or WriteCIFASCII(). mmdb return type
      int write_coordinates(const std::string &file_name) const; // return 0 on OK, 1 on failure

      std::string molecule_to_PDB_string() const;

      std::string molecule_to_mmCIF_string() const;
 
      std::vector<atom_spec_t> get_fixed_atoms() const;
 
      std::vector<std::string> chains_in_model() const;
      std::vector<std::pair<residue_spec_t, std::string> > get_single_letter_codes_for_chain(const std::string &chain_id) const;
 
      residue_spec_t get_residue_closest_to(mmdb::Manager *mol, const clipper::Coord_orth &co) const;
 
      std::vector<std::string> get_chain_ids() const;

      std::vector<std::vector<std::string> > get_ncs_related_chains() const;

      bool copy_ncs_chain(const std::string &from_chain_id, const std::string &to_chain_id);

      std::vector<double> get_residue_CA_position(const std::string &cid) const;

      std::vector<double> get_residue_average_position(const std::string &cid) const;

      std::vector<double> get_residue_sidechain_average_position(const std::string &cid) const;

      void set_occupancy(const std::string &cid, float occ_new);
 
      // ----------------------- model bonds
 
      simple_mesh_t get_bonds_mesh(const std::string &mode, protein_geometry *geom,
                                   bool against_a_dark_background,
                                   float bonds_width, float atom_radius_to_bond_width_ratio,
                                   int smoothness_factor,
                                   bool draw_hydrogen_atoms_flag,
                                   bool draw_missing_residue_loops);
 
      simple_mesh_t get_goodsell_style_mesh(protein_geometry *geom_p, float colour_wheel_rotation_step,
                                            float saturation, float goodselliness);
 
      instanced_mesh_t get_bonds_mesh_instanced(const std::string &mode, protein_geometry *geom,
                                                bool against_a_dark_background,
                                                float bonds_width, float atom_radius_to_bond_width_ratio,
                                                bool render_atoms_as_aniso, // if possible, of course
                                                float aniso_probability,
                                                bool render_aniso_atoms_as_ortep,
                                                int smoothness_factor,
                                                bool draw_hydrogen_atoms_flag,
                                                bool draw_missing_residue_loops);
 
      instanced_mesh_t get_bonds_mesh_for_selection_instanced(const std::string &mode, const std::string &selection_cid,
                                                              protein_geometry *geom,
                                                              bool against_a_dark_background,
                                                              float bonds_width, float atom_radius_to_bond_width_ratio,
                                                              bool render_atoms_as_aniso, // if possible, of course
                                                              bool render_aniso_atoms_as_ortep,
                                                              int smoothness_factor,
                                                              bool draw_hydrogen_atoms_flag,
                                                              bool draw_missing_residue_loops);
 
      instanced_mesh_t get_goodsell_style_mesh_instanced(protein_geometry *geom_p, float colour_wheel_rotation_step,
                                                         float saturation, float goodselliness);
 
 
      // adding colours using the functions below add into user_defined_colours
      std::map<unsigned int, colour_holder> user_defined_bond_colours;
 
      // we store these variables so that they can be used by (temporary) molecules constructed from atom selections
      //
      std::vector<std::pair<std::string, unsigned int> > indexed_user_defined_colour_selection_cids;
      bool indexed_user_defined_colour_selection_cids_apply_to_non_carbon_atoms_also;

      void set_user_defined_bond_colours(const std::map<unsigned int, std::array<float, 4> > &colour_map);

      // make this static?
      void set_user_defined_atom_colour_by_selections(const std::vector<std::pair<std::string, unsigned int> > &indexed_residues_cids,
                                                      bool colour_applies_to_non_carbon_atoms_also,
                                                      mmdb::Manager *mol);
 
      // need not be public
      void store_user_defined_atom_colour_selections(const std::vector<std::pair<std::string, unsigned int> > &indexed_residues_cids,
                                                     bool colour_applies_to_non_carbon_atoms_also);
 
      void apply_user_defined_atom_colour_selections(const std::vector<std::pair<std::string, unsigned int> > &indexed_residues_cids,
                                                     bool colour_applies_to_non_carbon_atoms_also,
                                                     mmdb::Manager *mol);

      void set_colour_wheel_rotation_base(float r);
 
      colour_holder base_colour_for_bonds;

      void set_base_colour_for_bonds(float r, float g, float b);
 
      std::set<int> no_bonds_to_these_atom_indices;
 
      void add_to_non_drawn_bonds(const std::string &atom_selection_cid);
 
      void clear_non_drawn_bonds() { no_bonds_to_these_atom_indices.clear(); }
 
      void print_non_drawn_bonds() const;
 
      void fill_default_colour_rules(); // assign colours to chains.

      std::vector<std::pair<std::string, std::string> > colour_rules;

      void add_colour_rule(const std::string &selection, const std::string &colour_name);

      void delete_colour_rules();
 
      void print_colour_rules() const;

      std::vector<std::pair<std::string, std::string> > get_colour_rules() const;
 
      std::vector<std::pair<std::string, float> > M2T_float_params;
      std::vector<std::pair<std::string, int> >   M2T_int_params;

      void M2T_updateFloatParameter(const std::string &param_name, float value);

      void M2T_updateFloatParameter(const std::string &param_name, int value);
 
      void print_M2T_FloatParameters() const;
 
      void print_M2T_IntParameters() const;

      void M2T_updateIntParameter(const std::string &param_name, int value);
 
      simple_mesh_t get_molecular_representation_mesh(const std::string &cid,
                                                      const std::string &colour_scheme,
                                                      const std::string &style,
                                                      int secondaryStructureUsageFlag) const;
 
      simple_mesh_t get_gaussian_surface(float sigma, float contour_level,
                                         float box_radius, float grid_scale, float fft_b_factor) const;
 
      simple_mesh_t get_chemical_features_mesh(const std::string &cid, const protein_geometry &geom) const;
 
      bool hydrogen_atom_should_be_drawn() const { return false; } // 20221018-PE for now.
      void set_use_bespoke_carbon_atom_colour(bool state) {
         use_bespoke_grey_colour_for_carbon_atoms = state;
         // make_bonds_type_checked("set_use_bespoke_carbon_atom_colour");
      }
      void set_bespoke_carbon_atom_colour(const colour_t &col) {
         bespoke_carbon_atoms_colour = col;
         // make_bonds_type_checked("set_bespoke_carbon_atom_colour");
      }

      void export_map_molecule_as_gltf(clipper::Coord_orth &position,
                                       float radius, float contour_level,
                                       const std::string &file_name);

      void export_model_molecule_as_gltf(const std::string &mode,
                                         const std::string &selection_cid,
                                         protein_geometry *geom,
                                         bool against_a_dark_background,
                                         float bonds_width, float atom_radius_to_bond_width_ratio, int smoothness_factor,
                                         bool draw_hydrogen_atoms_flag, bool draw_missing_residue_loops,
                                         const std::string &file_name);
 
      // this is the ribbons and surfaces API
      void export_molecular_representation_as_gltf(const std::string &atom_selection_cid,
                                                  const std::string &colour_scheme,
                                                  const std::string &style,
                                                  int secondary_structure_usage_flag,
                                                  const std::string &file_name);
 
      void export_chemical_features_as_gltf(const std::string &cid,
                                            const protein_geometry &geom,
                                            const std::string &file_name) const;
 
      float gltf_pbr_roughness;
      float gltf_pbr_metalicity;
 
      void set_show_symmetry(bool f) { show_symmetry = f;}
      bool get_show_symmetry() { return show_symmetry;}
      void transform_by(mmdb::mat44 SSMAlign_TMatrix);
      void transform_by(const clipper::RTop_orth &rtop, mmdb::Residue *res);
      void transform_by(const clipper::RTop_orth &rtop);
 
      symmetry_info_t get_symmetry(float symmetry_search_radius, const Cartesian &symm_centre) const;
 
      // ----------------------- model analysis functions
 
      std::vector<std::string> non_standard_residue_types_in_model() const;
      std::vector<phi_psi_prob_t> ramachandran_validation(const ramachandrans_container_t &rc) const;
      // not const because it recalculates the bonds.
      simple_mesh_t get_rotamer_dodecs(protein_geometry *geom_p, rotamer_probability_tables *rpt);
 
      instanced_mesh_t get_rotamer_dodecs_instanced(protein_geometry *geom_p, rotamer_probability_tables *rpt);
 
      omega_distortion_info_container_t peptide_omega_analysis(const protein_geometry &geom,
                                                               const std::string &chain_id,
                                                               bool mark_cis_peptides_as_bad_flag) const;
 
      std::vector<residue_spec_t> get_non_standard_residues_in_molecule() const;
 
      std::vector<std::string> get_residue_types_without_dictionaries(const protein_geometry &geom) const;

      instanced_mesh_t contact_dots_for_ligand(const std::string &cid, const protein_geometry &geom,
                                               unsigned int num_subdivisions) const;

      instanced_mesh_t all_molecule_contact_dots(const coot::protein_geometry &geom,
                                                 unsigned int num_subdivisions) const;
 
      generic_3d_lines_bonds_box_t
      make_exportable_environment_bond_box(coot::residue_spec_t &spec, float max_dist, coot::protein_geometry &geom) const;

      simple::molecule_t get_simple_molecule(int imol, const std::string &residue_cid,
                                             const bool draw_hydrogen_atoms_flag,
                                             coot::protein_geometry *geom_p);
      // which call this function:
      simple::molecule_t get_simple_molecule(int imol, mmdb::Residue *residue_p,
                                             bool draw_hydrogen_atoms_flag,
                                             coot::protein_geometry *geom_p);

      // We need the thread pool?
      coot::simple_mesh_t get_mesh_for_ligand_validation_vs_dictionary(const std::string &ligand_cid,
                                                                       coot::protein_geometry &geom,
                                                                       ctpl::thread_pool &static_thread_pool);

      std::vector<coot::geometry_distortion_info_container_t>
      geometric_distortions_for_one_residue_from_mol(const std::string &ligand_cid, bool with_nbcs,
                                                     coot::protein_geometry &geom,
                                                     ctpl::thread_pool &static_thread_pool);

      std::vector<coot::geometry_distortion_info_container_t>
      geometric_distortions_for_selection_from_mol(const std::string &selection_cid, bool with_nbcs,
                                                   coot::protein_geometry &geom,
                                                   ctpl::thread_pool &static_thread_pool);
 
      // I want a function that does the evaluation of the distortion
      // in place - I don't want to get a function that allows me to
      // calculate the distortion from the restraints.
      //
      std::pair<int, double>
      simple_geometric_distortions_from_mol(const std::string &ligand_cid, bool with_nbcs,
                                            coot::protein_geometry &geom,
                                            ctpl::thread_pool &static_thread_pool);
 
      coot::instanced_mesh_t get_extra_restraints_mesh(int mode) const;

      std::vector<coot::residue_spec_t> residues_near_residue(const std::string &residue_cid, float dist) const;

     std::vector<coot::atom_distance_t>
     get_distances_between_atoms_of_residues(const std::string &cid_res_1,
                         const std::string &cid_res_2,
                         float dist_max) const;

      std::vector<plain_atom_overlap_t> get_overlaps(protein_geometry *geom_p);

      float get_atom_overlap_score(protein_geometry *geom_p) const;

      std::vector<plain_atom_overlap_t> get_overlaps_for_ligand(const std::string &cid_ligand,
                                                                protein_geometry *geom_p);

      coot::atom_overlaps_dots_container_t get_overlap_dots(protein_geometry *geom_p);

      coot::atom_overlaps_dots_container_t get_overlap_dots_for_ligand(const std::string &cid_ligand,
                                                                       protein_geometry *geom_p);
 
      instanced_mesh_t get_HOLE(const clipper::Coord_orth &start_pos,
                                const clipper::Coord_orth &end_pos,
                                const protein_geometry &geom) const;

      std::string get_svg_for_2d_ligand_environment_view(const std::string &residue_cid,
                                                         protein_geometry *geom,
                                                         bool add_key) const;
 
 
#ifdef MAKE_ENHANCED_LIGAND_TOOLS
      RDKit::ROMol *rdkit_mol(const std::string &ligand_cid);
#endif
 
      // ------------------------ model-changing functions
 
      int move_molecule_to_new_centre(const coot::Cartesian &new_centre);
      coot::Cartesian get_molecule_centre() const;
 
      int flip_peptide(const atom_spec_t &rs, const std::string &alt_conf);
      int auto_fit_rotamer(const std::string &chain_id, int res_no, const std::string &ins_code,
                           const std::string &alt_conf,
                           const clipper::Xmap<float> &xmap, const coot::protein_geometry &pg);
 
      std::pair<bool,float> backrub_rotamer(mmdb::Residue *residue_p,
                                            const clipper::Xmap<float> &xmap,
                                            const coot::protein_geometry &pg);
 
      std::pair<bool,float> backrub_rotamer(const std::string &chain_id, int res_no,
                                            const std::string &ins_code, const std::string &alt_conf,
                                            const clipper::Xmap<float> &xmap,
                                            const coot::protein_geometry &pg);
 
      // return the number of deleted atoms
      int delete_atoms(const std::vector<atom_spec_t> &atoms);
      int delete_atom(atom_spec_t &atom_spec);
      int delete_residue(residue_spec_t &residue_spec);
      int delete_residue_atoms_with_alt_conf(coot::residue_spec_t &residue_spec, const std::string &alt_conf);
      int delete_chain_using_atom_cid(const std::string &cid);
      int delete_literal_using_cid(const std::string &cid); // cid is an atom selection, e.g. containing a residue range
 
      int change_alt_locs(const std::string &cid, const std::string &change_mode);
 
      std::pair<int, std::string> add_terminal_residue_directly(const residue_spec_t &spec,
                                                                const std::string &new_res_type,
                                                                const protein_geometry &geom,
                                                                const clipper::Xmap<float> &xmap,
                                                                mmdb::Manager *standard_residues_asc_mol, // for RNA
                                                                ctpl::thread_pool &static_thread_pool);
 
      void execute_simple_nucleotide_addition(const std::string &term_type,
                                              mmdb::Residue *res_p, const std::string &chain_id,
                                              mmdb::Manager *standard_residues_asc_mol);
      void execute_simple_nucleotide_addition(mmdb::Residue *residue_p,
                                              mmdb::Manager *standard_residues_asc_mol);
      void execute_simple_nucleotide_addition(const std::string &cid,
                                              mmdb::Manager *standard_residues_asc_mol);
 
      int add_compound(const dictionary_residue_restraints_t &monomer_restraints, const Cartesian &position,
                       const clipper::Xmap<float> &xmap, float map_rmsd);
 

      int add_alternative_conformation(const std::string &cid);

      int fill_partial_residue(const residue_spec_t &res_spec, const std::string &alt_conf,
                               const clipper::Xmap<float> &xmap, const protein_geometry &geom);

      int fill_partial_residues(const clipper::Xmap<float> &xmap, protein_geometry *geom);
 
      int mutate(const residue_spec_t &spec, const std::string &new_res_type);
 
      void add_named_glyco_tree(const std::string &glycosylation_name, const std::string &chain_id, int res_no,
                                const clipper::Xmap<float> &xmap, protein_geometry *geom);
 
      int side_chain_180(const residue_spec_t &residue_spec, const std::string &alt_conf,
                         coot::protein_geometry *geom_p); // sub functions are non-const
 
      int delete_side_chain(const residue_spec_t &residue_spec);
 
      std::string jed_flip(coot::residue_spec_t &spec, const std::string &atom_name, const std::string &alt_conf,
                           bool invert_selection, protein_geometry *geom);
 
      // move this up
      std::string jed_flip_internal(coot::atom_tree_t &tree,
                                    const std::vector<coot::dict_torsion_restraint_t> &interesting_torsions,
                                    const std::string &atom_name,
                                    bool invert_selection);
 
      // return a non-null string on a problem
      std::string jed_flip_internal(coot::atom_tree_t &tree,
                                    const dict_torsion_restraint_t &torsion,
                                    const std::string &atom_name,
                                    bool invert_selection);
 
      // manipulate the torsion angles of first residue in this molecule to
      // match those of the passed (reference residue (from a different
      // molecule, typically). This function presumes that this molecule
      // contains just a ligand.
      // @return the number of torsion angles changed
      int match_torsions(mmdb::Residue *res_ref,
                       const std::vector <coot::dict_torsion_restraint_t> &tr_ligand,
                       const coot::protein_geometry &geom);
 
      coot::minimol::molecule eigen_flip_residue(const residue_spec_t &residue_spec);
 
      int apply_transformation_to_atom_selection(const std::string &atom_selection_cid,
                                                 int n_atoms_in_selection,
                                                 clipper::Coord_orth &rotation_centre,
                                                 clipper::RTop_orth &rtop);

      void multiply_residue_temperature_factors(const std::string &cid, float factor);

      int add_hydrogen_atoms(protein_geometry *geom); // because of coot::reduce api - hmm.

      int delete_hydrogen_atoms();

      bool delete_all_carbohydrate();

      bool residue_is_nucleic_acid(const std::string &cid) const;
 
      // change the chain id
      // return -1 on a conflict
      // 1 on good.
      // 0 on did nothing
      // return also an information/error message
      std::pair<int, std::string> change_chain_id(const std::string &from_chain_id,
                                                  const std::string &to_chain_id,
                                                  bool use_resno_range,
                                                  int start_resno, int end_resno);
 
      // make these private
      //
      std::pair<int, std::string>
      change_chain_id_with_residue_range(const std::string &from_chain_id,
                                         const std::string &to_chain_id,
                                         int start_resno,
                                         int end_resno);
      void change_chain_id_with_residue_range_helper_insert_or_add(mmdb::Chain *to_chain_p, mmdb::Residue *new_residue);

      int new_positions_for_residue_atoms(const std::string &residue_cid, const std::vector<api::moved_atom_t> &moved_atoms);

      int new_positions_for_atoms_in_residues(const std::vector<api::moved_residue_t> &moved_residues);

      int new_positions_for_residue_atoms(mmdb::Residue *residue_p, const std::vector<api::moved_atom_t> &moved_atoms,
                                          bool do_backup);

      int merge_molecules(const std::vector<mmdb::Manager *> &mols);
 
      // My ligands don't jiggle-jiggle...
      //
      // Hey, what do you know, they actually do.
      float fit_to_map_by_random_jiggle(const residue_spec_t &res_spec, const clipper::Xmap<float> &xmap, float map_rmsd,
                                        int n_trials, float translation_scale_factor);

      float fit_to_map_by_random_jiggle_using_atom_selection(const std::string &cid, const clipper::Xmap<float> &xmap, float map_rmsd,
                                        int n_trials, float translation_scale_factor);
 
      int cis_trans_conversion(const std::string &atom_cid, mmdb::Manager *standard_residues_mol);
 
      int replace_residue(const std::string &residue_cid, const std::string &new_residue_type, int imol_enc,
                          const protein_geometry &geom);
 
      // the above is a wrapper for this:
      // (which was a scripting function and now has been moved into coot utils)
      int mutate_by_overlap(mmdb::Residue *residue_p, const dictionary_residue_restraints_t &restraints);

      int replace_fragment(atom_selection_container_t asc);
 
      // replace the atoms of SelHnd, which is a selection of mol_ref into this molecule.
      // Use old_atom_index_handle for fast indexing.
      int replace_fragment(mmdb::Manager *mol_ref, int old_atom_index_handle, int SelHnd);

      class rotamer_change_info_t {
         public:
         int rank;
         std::string name;
         float richardson_probability;
         int status;
         rotamer_change_info_t(int rank, const std::string &name, float rp, int status) : rank(rank), name(name), richardson_probability(rp), status(status) {}
         rotamer_change_info_t() : rank(-1), name(""), richardson_probability(-1), status(0) {}
      };

      rotamer_change_info_t change_to_next_rotamer(const coot::residue_spec_t &res_spec, const std::string &alt_conf, const coot::protein_geometry &pg);
 
      rotamer_change_info_t change_to_previous_rotamer(const coot::residue_spec_t &res_spec, const std::string &alt_conf, const coot::protein_geometry &pg);
 
      rotamer_change_info_t change_to_first_rotamer(const coot::residue_spec_t &res_spec, const std::string &alt_conf, const coot::protein_geometry &pg);
 
      // rotamer_change_direction is  1 for increase rotamer index
      // rotamer_change_direction is -1 for decrease rotamer index
      // rotamer_change_direction is  0 for change to 0th
      // index cycling is handled by the function
      //
      rotamer_change_info_t change_rotamer_number(const coot::residue_spec_t &res_spec, const std::string &alt_conf,
                                           int rotamer_change_direction,
                                           const coot::protein_geometry &pg);
 
      void associate_sequence_with_molecule(const std::string &chain_id, const std::string &sequence);

      void assign_sequence(const clipper::Xmap<float> &xmap, const coot::protein_geometry &geom);

      std::vector<std::pair<std::string, std::string> > get_sequence_info() const;

      chain_mutation_info_container_t get_mutation_info() const;
 
      // ----------------------- merge molecules
 
      // merge molecules helper functions
 
      bool is_het_residue(mmdb::Residue *residue_p) const;
      // return state, max_resno + 1, or 0, 1 of no residues in chain.
      //
      std::pair<short int, int> next_residue_number_in_chain(mmdb::Chain *w,
                                                             bool new_res_no_by_hundreds=false) const;
 
      mmdb::Residue *copy_and_add_residue_to_chain(mmdb::Chain *this_model_chain,
                                                   mmdb::Residue *add_model_residue,
                                                   bool new_resno_by_hundreds_flag=true);
      void copy_and_add_chain_residues_to_chain(mmdb::Chain *new_chain, mmdb::Chain *this_molecule_chain);
      std::vector<std::string> map_chains_to_new_chains(const std::vector<std::string> &adding_model_chains,
                                                        const std::vector<std::string> &this_model_chains) const;
      // that's too complicated for try_add_by_consolidation(), we just want this:
      std::string suggest_new_chain_id(const std::string &current_chain_id) const;
      std::pair<bool, std::vector<std::string> > try_add_by_consolidation(mmdb::Manager *adding_mol);
      bool merge_molecules_just_one_residue_homogeneous(atom_selection_container_t molecule_to_add);
      bool merge_molecules_just_one_residue_at_given_spec(atom_selection_container_t molecule_to_add,
                                                          residue_spec_t target_spec);
 
      // return success status and spec if new residue if possible.
      std::pair<bool, coot::residue_spec_t> merge_ligand_to_near_chain(mmdb::Manager *mol);
 
      // return success status and spec if new residue if possible.
      std::pair<int, std::vector<merge_molecule_results_info_t> >
      merge_molecules(const std::vector<atom_selection_container_t> &add_molecules);
 
 
      std::pair<int, double>
      get_torsion(const std::string &cid, const std::vector<std::string> &atom_names) const;
 
 
      void
      set_temperature_factors_using_cid(const std::string &cid, float temp_fact);
 
      // ----------------------- refinement
 
      coot::extra_restraints_t extra_restraints;

      int read_extra_restraints(const std::string &file_name);
      std::vector<mmdb::Residue *> select_residues(const residue_spec_t &spec, const std::string &mode) const;
      std::vector<mmdb::Residue *> select_residues(const std::string &chain_id, int resno_start, int resno_end) const;
      std::vector<mmdb::Residue *> select_residues(const std::string &multi_cid, const std::string &mode) const;

      int refine_direct(std::vector<mmdb::Residue *> rv, const std::string &alt_loc, const clipper::Xmap<float> &xmap,
                        unsigned int max_number_of_threads,
                        float map_weight, int n_cycles, const coot::protein_geometry &geom,
                        bool do_rama_plot_restraints, float rama_plot_weight,
                        bool do_torsion_restraints, float torsion_weight,
                        bool refinement_is_quiet);
 
      int minimize(const std::string &atom_selection_cid,
                   int n_cycles,
                   bool do_rama_plot_restraints, float rama_plot_weight,
                   bool do_torsion_restraints, float torsion_weight, bool refinement_is_quiet,
                   coot::protein_geometry *geom_p);
 
      bool shiftfield_b_factor_refinement(const clipper::HKL_data<clipper::data32::F_sigF> &F_sigF,
                                          const clipper::HKL_data<clipper::data32::Flag> &free_flag);
 
      void fix_atom_selection_during_refinement(const std::string &atom_selection_cid);
 
      // refine all of this molecule - the links and non-bonded contacts will be determined from mol_ref;
      void init_all_molecule_refinement(int imol_ref_mol, coot::protein_geometry &geom,
                                        const clipper::Xmap<float> &xmap, float map_weight,
                                        ctpl::thread_pool *thread_pool);
 
      // add or update.
      void add_target_position_restraint(const std::string &atom_cid, float pos_x, float pos_y, float pos_z);
 
      //
      void turn_off_when_close_target_position_restraint();
 
      std::vector<std::pair<mmdb::Atom *, clipper::Coord_orth> > atoms_with_position_restraints;
 
      instanced_mesh_t add_target_position_restraint_and_refine(const std::string &atom_cid, float pos_x, float pos_y, float pos_z,
                                                                int n_cyles,
                                                                coot::protein_geometry *geom_p);
      void clear_target_position_restraint(const std::string &atom_cid);

      int refine_using_last_restraints(int n_steps);
 
      // something is happening to this pointer - where is it being reset?
      restraints_container_t *get_last_restraints() { return last_restraints; }

      void clear_target_position_restraints();

      void clear_refinement();
 
      // make them yourself - easy as pie.
      void generate_self_restraints(float local_dist_max,
                                    const coot::protein_geometry &geom);
      void generate_chain_self_restraints(float local_dist_max,
                                          const std::string &chain_id,
                                          const coot::protein_geometry &geom);
      void generate_local_self_restraints(float local_dist_max,
                                          const std::vector<coot::residue_spec_t> &residue_specs,
                                          const coot::protein_geometry &geom);
      void generate_local_self_restraints(float local_dist_max,
                                          const std::string &multi_selection_cid,
                                          const coot::protein_geometry &geom);
      void generate_local_self_restraints(int selHnd, float local_dist_max,
                                          const coot::protein_geometry &geom);
 
      void add_parallel_plane_restraint(coot::residue_spec_t spec_1,
                                        coot::residue_spec_t spec_2);
 
      // which uses:
      std::vector<std::string> nucelotide_residue_name_to_base_atom_names(const std::string &rn) const;
      // for non-bases, normal amino acids (simple-minded, currently).
      std::vector<std::string> residue_name_to_plane_atom_names(const std::string &rn) const;
 
      void clear_extra_restraints();
 
      // --------------- rigid body fit
      int rigid_body_fit(const std::string &mult_cids, const clipper::Xmap<float> &xmap);
 
      int rotate_around_bond(const std::string &residue_cid,
                             const std::string &alt_conf,
                             coot::atom_name_quad quad,
                             double torsion_angle, protein_geometry &geom);
 
      // ----------------------- map functions
 
      void scale_map(float scale_factor);
 
      bool is_EM_map() const;
 
      float get_density_at_position(const clipper::Coord_orth &pos) const;
 
      // return -1.0 on not-a-map
      float get_map_mean() const;
      // return -1.1 on not-a-map
      float get_map_rmsd_approx() const;
      int write_map(const std::string &file_name) const;
      void set_map_is_difference_map(bool flag);
      bool is_difference_map_p() const;
 
      // gets updated in sfcalc_genmaps_using_bulk_solvent
      clipper::Xmap<float> updating_maps_previous_difference_map;
      // these are in the asymmetric unit
      std::vector<std::pair<clipper::Coord_orth, float> > updating_maps_diff_diff_map_peaks;
      void set_updating_maps_diff_diff_map_peaks(const std::vector<std::pair<clipper::Coord_orth, float> > &v) {
         updating_maps_diff_diff_map_peaks = v; }
      std::vector<std::pair<clipper::Coord_orth, float> > get_updating_maps_diff_diff_map_peaks(const clipper::Coord_orth &screen_centre) const;

      float get_suggested_initial_contour_level() const;
 
      // changes the internal map mesh holder (hence not const)
      simple_mesh_t get_map_contours_mesh(clipper::Coord_orth position, float radius, float contour_level,
                                          bool use_thread_pool, ctpl::thread_pool *thread_pool_p);
      simple_mesh_t get_map_contours_mesh_using_other_map_for_colours(const clipper::Coord_orth &position, float radius, float contour_level,
                                                                      const clipper::Xmap<float> &xmap);
      simple_mesh_t get_map_contours_mesh_using_other_map_for_colours(const clipper::Coord_orth &position, float radius, float contour_level,
                                      const user_defined_colour_table_t &udct,
                                                                      const clipper::Xmap<float> &xmap);

      class histogram_info_t {
      public:
         float base;
         float bin_width;
         std::vector<int> counts;
         float mean;
         float variance;
         histogram_info_t() : base(-1), bin_width(-1), mean(-1), variance(-1) {}
         histogram_info_t(float min_density, float bw, const std::vector<int> &c) :
            base(min_density), bin_width(bw), counts(c), mean(-1), variance(-1)  {}
      };

      histogram_info_t get_map_histogram(unsigned int n_bins, float zoom_factor) const;
 
      // just look at the vertices of the map - not the whole thing
      // Sample the points from other_map
      histogram_info_t
      get_map_vertices_histogram(const clipper::Xmap<float> &other_xmap,
                 const clipper::Coord_orth &pt,
                 float radius, float contour_level,
                 bool use_thread_pool, ctpl::thread_pool *thread_pool_p,
                 unsigned int n_bins);
 
      void set_map_colour(colour_holder holder);
      void set_map_colour_saturation(float s) { radial_map_colour_saturation = s; }

      void set_other_map_for_colouring_min_max(float min_v, float max_v);
      void set_other_map_for_colouring_invert_colour_ramp(bool state) {
         radial_map_colour_invert_flag = state;
      }
 
      double sum_density_for_atoms_in_residue(const std::string &cid,
                                              const std::vector<std::string> &atom_names,
                                              const clipper::Xmap<float> &xmap) const;

      class interesting_place_t {
      public:
         std::string feature_type;
         residue_spec_t residue_spec; // use this for sorting a combination of interesting_place_t types.
         float x, y, z;
         std::string button_label;
         float feature_value; // e.g. peak-height (not all "interesting" feature values can be captured by a float of course)
         float badness; // a nubmer between 100.0 and 0.0 (inclusive) if it's negative then it's not set.
         interesting_place_t() {}
         interesting_place_t(const std::string &feature_type, const residue_spec_t &rs, const clipper::Coord_orth &pt, const std::string &bl) :
            feature_type(feature_type), residue_spec(rs), button_label(bl) {
            x = pt.x(); y = pt.y(); z = pt.z();
            feature_value = -1; // something "unset"
            badness = -1.1; // "unset"
         }

         interesting_place_t(const std::string &feature_type, const clipper::Coord_orth &pt, const std::string &button_label) :
            feature_type(feature_type), button_label(button_label) {
            x = pt.x(); y = pt.y(); z = pt.z();
            feature_value = -1; // something "unset"
            badness = -1.1; // "unset"
         }

         void set_feature_value(const float &f) { feature_value = f; }
         void set_badness_value(const float &b) { badness = b; }
      };

      class difference_map_peaks_info_t {
      public:
         clipper::Coord_orth pos;
         float peak_height; // nrmsd
         // maybe other useful stuff here in future
         difference_map_peaks_info_t(const clipper::Coord_orth &p, float ph) : pos(p), peak_height(ph) {}
      };
 
      // the molecule is passed so that the peaks are placed around the protein
      std::vector<interesting_place_t> difference_map_peaks(mmdb::Manager *mol, float n_rmsd) const;
 
      texture_as_floats_t get_map_section_texture(int section_index, int axis,
                                                  float data_value_for_bottom, float data_value_for_top) const;

      int get_number_of_map_sections(int axis_id) const;
 
      // ---------------------------------- blender --------------------------------------
 
      blender_mesh_t blender_mesh;
      std::vector<float> get_vertices_for_blender() const;
      std::vector<int> get_triangles_for_blender() const;
      std::vector<float> get_colour_table_for_blender() const;
 
      // pass other things here
      void make_mesh_for_bonds_for_blender(const std::string &mode, protein_geometry *geom, bool against_a_dark_background,
                                      float bond_width, float atom_radius_to_bond_width_ratio,
                                      int smoothness_factor);

      void make_mesh_for_molecular_representation_for_blender(const std::string &cid,
                                                              const std::string &colour_scheme,
                                                              const std::string &style,
                                                              int secondary_structure_usage_flag);
 
      void make_mesh_for_goodsell_style_for_blender(protein_geometry *geom_p,
                                                    float colour_wheel_rotation_step,
                                                    float saturation,
                                                    float goodselliness);
 
      void make_mesh_for_map_contours_for_blender(Cartesian position, float contour_level, float radius);
      void make_mesh_for_gaussian_surface_for_blender(float sigma, float contour_level, float box_radius, float grid_scale,float b_factor);
   };
}
 
 
#endif // COOT_MOLECULE_HH