EmbeddedFrag.h

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//
//  Copyright (C) 2003-2022 Greg Landrum and other RDKit contributors
//
//   @@ All Rights Reserved @@
//  This file is part of the RDKit.
//  The contents are covered by the terms of the BSD license
//  which is included in the file license.txt, found at the root
//  of the RDKit source tree.
//
#include <RDGeneral/export.h>
#ifndef RD_EMBEDDED_FRAG_H
#define RD_EMBEDDED_FRAG_H
 
#include <RDGeneral/types.h>
#include <Geometry/Transform2D.h>
#include <Geometry/point.h>
#include "DepictUtils.h"
#include <boost/smart_ptr.hpp>
#include <boost/dynamic_bitset.hpp>
 
namespace RDKit {
class ROMol;
class Bond;
}  // namespace RDKit
 
namespace RDDepict {
typedef boost::shared_array<double> DOUBLE_SMART_PTR;
 
//! Class that contains the data for an atoms that has already been embedded
class RDKIT_DEPICTOR_EXPORT EmbeddedAtom {
 public:
  typedef enum {
    UNSPECIFIED = 0,
    CISTRANS,
    RING
  } EAtomType;
 
  EmbeddedAtom() { neighs.clear(); }
 
  EmbeddedAtom(const EmbeddedAtom &other) = default;
 
  EmbeddedAtom(unsigned int aid, const RDGeom::Point2D &pos)
      : aid(aid),
        angle(-1.0),
        nbr1(-1),
        nbr2(-1),
        CisTransNbr(-1),
        ccw(true),
        rotDir(0),
        d_density(-1.0),
        df_fixed(false) {
    loc = pos;
  }
 
  EmbeddedAtom &operator=(const EmbeddedAtom &other) {
    if (this == &other) {
      return *this;
    }
 
    aid = other.aid;
    loc = other.loc;
    angle = other.angle;
    nbr1 = other.nbr1;
    nbr2 = other.nbr2;
    CisTransNbr = other.CisTransNbr;
    rotDir = other.rotDir;
    normal = other.normal;
    ccw = other.ccw;
    neighs = other.neighs;
    d_density = other.d_density;
    df_fixed = other.df_fixed;
    return *this;
  }
 
  void Transform(const RDGeom::Transform2D &trans) {
    RDGeom::Point2D temp = loc + normal;
    trans.TransformPoint(loc);
    trans.TransformPoint(temp);
    normal = temp - loc;
  }
 
  void Reflect(const RDGeom::Point2D &loc1, const RDGeom::Point2D &loc2) {
    RDGeom::Point2D temp = loc + normal;
    loc = reflectPoint(loc, loc1, loc2);
    temp = reflectPoint(temp, loc1, loc2);
    normal = temp - loc;
    ccw = (!ccw);
  }
 
  unsigned int aid{0};  // the id of the atom
 
  //! the angle that is already takes at this atom, so any new atom attaching to
  /// this atom with have to fall in the available part
  double angle{-1.0};
 
  //! the first neighbor of this atom that form the 'angle'
  int nbr1{-1};
 
  //! the second neighbor of atom that from the 'angle'
  int nbr2{-1};
 
  //! is this is a cis/trans atom the neighbor of this atom that is involved in
  /// the cis/trans system - defaults to -1
  int CisTransNbr{-1};
 
  //! which direction do we rotate this normal to add the next bond
  //! if ccw is true we rotate counter clockwise, otherwise rotate clock wise,
  /// by an angle that is <= PI/2
  bool ccw{true};
 
  //! rotation direction around this atom when adding new atoms,
  /// we determine this for the first neighbor and stick to this direction
  /// after that
  //! useful only on atoms that are degree >= 4
  int rotDir{0};
 
  RDGeom::Point2D loc;  // the current location of this atom
  //! this is a normal vector to one of the bonds that added this atom
  //! it provides the side on which we want to add a new bond to this atom
  //! this is only relevant when we are dealing with non ring atoms. We would
  /// like to draw chains in a zig-zag manner
  RDGeom::Point2D normal;
 
  //! and these are the atom IDs of the neighbors that still need to be embedded
  RDKit::INT_VECT neighs;
 
  // density of the atoms around this atoms
  // - this is sum of inverse of the square of distances to other atoms from
  //   this atom. Used in the collision removal code
  // - initialized to -1.0
  double d_density{-1.0};
 
  //! if set this atom is fixed: further operations on the fragment may not
  //! move it.
  bool df_fixed{false};
};
 
typedef std::map<unsigned int, EmbeddedAtom> INT_EATOM_MAP;
typedef INT_EATOM_MAP::iterator INT_EATOM_MAP_I;
typedef INT_EATOM_MAP::const_iterator INT_EATOM_MAP_CI;
 
//! Class containing a fragment of a molecule that has already been embedded
/*
  Here is how this class is designed to be used
  - find a set of fused rings and compute the coordinates for the atoms in those
    ring
  - them grow this system either by adding non ring neighbors
  - or by adding other embedded fragment
  - so at the end of the process  the whole molecule end up being one these
    embedded frag objects
*/
class RDKIT_DEPICTOR_EXPORT EmbeddedFrag {
  // REVIEW: think about moving member functions up to global level and just
  // using
  // this class as a container
 
 public:
  //! Default constructor
  EmbeddedFrag() {
    d_eatoms.clear();
    d_attachPts.clear();
  }
 
  //! Initializer from a single atom id
  /*!
    A single Embedded Atom with this atom ID is added and placed at the origin
  */
  EmbeddedFrag(unsigned int aid, const RDKit::ROMol *mol);
 
  //! Constructor when the coordinates have been specified for a set of atoms
  /*!
     This simply initialized a set of EmbeddedAtom to have the same coordinates
     as the one's specified. No testing is done to verify any kind of
     correctness. Also this fragment is less ready (to expand and add new
     neighbors) than when using other constructors. This is because:
     - the user may have specified coords for only a part of the atoms in a
       fused ring systems in which case we need to find these atoms and merge
       these ring systems to this fragment
     - The atoms are not yet aware of their neighbor (what is left to add etc.)
       this again depends on  atoms properly so that new neighbors can be added
       to them
  */
  EmbeddedFrag(const RDKit::ROMol *mol,
               const RDGeom::INT_POINT2D_MAP &coordMap);
 
  //! Initializer from a set of fused rings
  /*!
    ARGUMENTS:
    \param mol        the molecule of interest
    \param fusedRings a vector of rings, each ring is a list of atom ids
    \param useRingTemplates whether to use ring system templates for generating
      initial coordinates
  */
  EmbeddedFrag(const RDKit::ROMol *mol, const RDKit::VECT_INT_VECT &fusedRings,
               bool useRingTemplates);
 
  //! Initializer for a cis/trans system using the double bond
  /*!
    ARGUMENTS:
    \param dblBond   the double bond that is involved in the cis/trans
    configuration
  */
  explicit EmbeddedFrag(const RDKit::Bond *dblBond);
 
  //! Expand this embedded system by adding neighboring atoms or other embedded
  /// systems
  /*!
 
    Note that both nratms and efrags are modified in this function
    as we start merging them with the current fragment
 
  */
  void expandEfrag(RDKit::INT_LIST &nratms, std::list<EmbeddedFrag> &efrags);
 
  //! Add a new non-ring atom to this object
  /*
    ARGUMENTS:
    \param aid     ID of the atom to be added
    \param toAid   ID of the atom that is already in this object to which this
    atom is added
  */
  void addNonRingAtom(unsigned int aid, unsigned int toAid);
 
  //! Merge this embedded object with another embedded fragment
  /*!
 
    The transformation (rotation + translation required to attached
    the passed in object will be computed and applied. The
    coordinates of the atoms in this object will remain fixed We
    will assume that there are no common atoms between the two
    fragments to start with
 
    ARGUMENTS:
    \param  embObj  another EmbeddedFrag object to be merged with this object
    \param  toAid   the atom in this embedded fragment to which the new object
    will be attached
    \param  nbrAid  the atom in the other fragment to attach to
  */
  void mergeNoCommon(EmbeddedFrag &embObj, unsigned int toAid,
                     unsigned int nbrAid);
 
  //! Merge this embedded object with another embedded fragment
  /*!
 
    The transformation (rotation + translation required to attached
    the passed in object will be computed and applied. The
    coordinates of the atoms in this object will remain fixed This
    already know there are a atoms in common and we will use them to
    merge things
 
    ARGUMENTS:
    \param embObj    another EmbeddedFrag object to be merged with this object
    \param commAtms  a vector of ids of the common atoms
 
  */
  void mergeWithCommon(EmbeddedFrag &embObj, RDKit::INT_VECT &commAtms);
 
  void mergeFragsWithComm(std::list<EmbeddedFrag> &efrags);
 
  //! Mark this fragment to be done for final embedding
  void markDone() { d_done = true; }
 
  //! If this fragment done for the final embedding
  bool isDone() { return d_done; }
 
  //! Get the molecule that this embedded fragment belongs to
  const RDKit::ROMol *getMol() const { return dp_mol; }
 
  //! Find the common atom ids between this fragment and a second one
  RDKit::INT_VECT findCommonAtoms(const EmbeddedFrag &efrag2);
 
  //! Find a neighbor to a non-ring atom among the already embedded atoms
  /*!
    ARGUMENTS:
    \param aid  the atom id of interest
 
    RETURNS:
    \return the id of the atom if we found a neighbor
                 -1 otherwise
 
    NOTE: by definition we can have only one neighbor in the embedded system.
  */
  int findNeighbor(unsigned int aid);
 
  //! Transform this object to a new coordinates system
  /*!
    ARGUMENTS:
    \param trans : the transformation that need to be applied to the atoms in
    this object
  */
  void Transform(const RDGeom::Transform2D &trans);
 
  void Reflect(const RDGeom::Point2D &loc1, const RDGeom::Point2D &loc2);
 
  const INT_EATOM_MAP &GetEmbeddedAtoms() const { return d_eatoms; }
 
  void Translate(const RDGeom::Point2D &shift) {
    INT_EATOM_MAP_I eari;
    for (eari = d_eatoms.begin(); eari != d_eatoms.end(); eari++) {
      eari->second.loc += shift;
    }
  }
 
  EmbeddedAtom GetEmbeddedAtom(unsigned int aid) const {
    INT_EATOM_MAP_CI posi = d_eatoms.find(aid);
    if (posi == d_eatoms.end()) {
      PRECONDITION(0, "Embedded atom does not contain embedded atom specified");
    }
    return posi->second;
  }
 
  //! the number of atoms in the embedded system
  int Size() const { return d_eatoms.size(); }
 
  //! \brief compute a box that encloses the fragment
  void computeBox();
 
  //! \brief Flip atoms on one side of a bond - used in removing collisions
  /*!
    ARGUMENTS:
    \param bondId - the bond used as the mirror to flip
    \param flipEnd - flip the atoms at the end of the bond
 
  */
  void flipAboutBond(unsigned int bondId, bool flipEnd = true);
 
  //! \brief flip one ring of a spiro compound to resolve collisions
  /*!
    \param spiroAid - the spiro center atom index
  */
  void flipAboutSpiroCenter(unsigned int spiroAid);
 
  void openAngles(const double *dmat, unsigned int aid1, unsigned int aid2);
 
  //! Find atom clashes and, optionally, non-adjacent bond intersections.
  //! Bonded atom pairs can be excluded when shortened bonds are expected.
  std::vector<PAIR_I_I> findCollisions(const double *dmat,
                                       bool includeBonds = true,
                                       bool includeBondedAtoms = true);
 
  void computeDistMat(DOUBLE_SMART_PTR &dmat);
 
  double mimicDistMatAndDensityCostFunc(const DOUBLE_SMART_PTR *dmat,
                                        double mimicDmatWt);
 
  void permuteBonds(unsigned int aid, unsigned int aid1, unsigned int aid2);
 
  void randomSampleFlipsAndPermutations(unsigned int nBondsPerSample = 3,
                                        unsigned int nSamples = 100,
                                        int seed = 100,
                                        const DOUBLE_SMART_PTR *dmat = nullptr,
                                        double mimicDmatWt = 0.0,
                                        bool permuteDeg4Nodes = false);
 
  //! Remove collisions in a structure by flipping rotatable bonds and spiro centers
  //! along the shortest path between two colliding atoms
  void removeCollisionsBondAndSpiroFlip();
  
  [[deprecated("please use removeCollisionsBondAndSpiroFlip()")]] void removeCollisionsBondFlip() { removeCollisionsBondAndSpiroFlip(); };
 
  //! Remove collision by opening angles at the offending atoms
  void removeCollisionsOpenAngles();
 
  //! Remove collisions by shortening bonds along the shortest path between the
  /// atoms
  void removeCollisionsShortenBonds();
 
  //! Remove collisions by expanding angles along the path between colliding atoms
  //! Runs after bond flipping, angle opening, and bond shortening.
  //! Only expands angles where the three atoms (prev-center-next) are NOT all
  //! in the same ring, preserving ring geometry while allowing ring-chain expansion.
  void removeCollisionsPathAngleExpansion();
 
  //! helpers functions to
 
  //! \brief make list of neighbors for each atom in the embedded system that
  //!  still need to be embedded
  void setupNewNeighs();
 
  //! update the unembedded neighbor atom list for a specified atom
  void updateNewNeighs(unsigned int aid);
 
  //! \brief Find all atoms in this embedded system that are
  //!  within a specified distant of a point
  int findNumNeigh(const RDGeom::Point2D &pt, double radius);
 
  inline double getBoxPx() { return d_px; }
  inline double getBoxNx() { return d_nx; }
  inline double getBoxPy() { return d_py; }
  inline double getBoxNy() { return d_ny; }
 
  void canonicalizeOrientation();
 
 private:
  double totalDensity();
 
  // Helper methods for collision resolution
  bool tryResolvingCollisionWithBondFlip(
      const std::pair<unsigned int, unsigned int> &cAids,
      unsigned int ncols,
      double prevDensity,
      std::map<int, unsigned int> &doneBonds,
      const double *dmat);
 
  bool tryResolvingCollisionWithSpiroFlip(
      const std::pair<unsigned int, unsigned int> &cAids,
      unsigned int ncols,
      double prevDensity,
      std::map<int, unsigned int> &doneSpiros,
      const boost::dynamic_bitset<> &spiroCenters,
      const double *dmat);
 
  // Helper methods for path angle expansion collision resolution
 
  //! Get all atoms on one side of a bond/angle, using BFS traversal
  //! \param center - the center atom (pivot point)
  //! \param sideStart - starting atom on the side to collect
  //! \param exclude - atom on the opposite side (don't cross to this side)
  //! \return vector of atom indices on the sideStart side
  std::vector<unsigned int> getAtomsOnSide(unsigned int center,
                                            unsigned int sideStart,
                                            unsigned int exclude);
 
  //! Open an angle by rotating one side around the center atom
  //! Makes the angle LARGER (closer to 180°) to expand the chain
  //! \param prevAtom - first atom forming the angle
  //! \param centerAtom - center atom (pivot point for rotation)
  //! \param nextAtom - second atom forming the angle
  //! \param angleIncrement - amount to open the angle (radians)
  //! \param dmat - distance matrix (for reference)
  //! \return true if a side could be rotated without moving fixed atoms or
  //! distorting a cycle
  bool openAngleByIncrement(unsigned int prevAtom,
                            unsigned int centerAtom,
                            unsigned int nextAtom,
                            double angleIncrement,
                            const double *dmat);
 
  // returns true if fused rings found a template
  bool matchToTemplate(const RDKit::INT_VECT &ringSystemAtoms);
 
  void embedFusedRings(const RDKit::VECT_INT_VECT &fusedRings,
                       bool useRingTemplates);
 
  void setupAttachmentPoints();
 
  //! \brief Find a transform to join a ring to the current embedded frag when
  /// we
  //! have only on common atom
  /*!
    So this is the state of affairs assumed here:
    - we already have some rings in the fused system embedded and the
      coordinates for the atoms
    - the coordinates for the atoms in the new ring (with the center
      of rings at the origin) are available nringCors. we want to
      translate and rotate this ring to join with the already
      embeded rings.
    - only one atom is common between this new ring and the atoms
      that are already embedded
    - so we need to compute a transform that includes a translation
      so that the common atom overlaps and the rotation to minimize
      overlap with other atoms.
 
    Here's what is done:
    - we bisect the remaining sweep angle at the common atom and
      attach the new ring such that the center of the new ring falls
      on this bisecting line
 
    NOTE: It is assumed here that the original coordinates for the
    new ring are such that the center is at the origin (this is the
    way rings come out of embedRing)
  */
  RDGeom::Transform2D computeOneAtomTrans(unsigned int commAid,
                                          const EmbeddedFrag &other);
 
  RDGeom::Transform2D computeTwoAtomTrans(
      unsigned int aid1, unsigned int aid2,
      const RDGeom::INT_POINT2D_MAP &nringCor);
 
  //! Merge a ring with already embedded atoms
  /*!
    It is assumed that the new rings has already been oriented
    correctly etc.  This function just update all the relevant data,
    like the neighbor information and the sweep angle
  */
  void mergeRing(const EmbeddedFrag &embRing, unsigned int nCommon,
                 const RDKit::INT_VECT &pinAtoms);
 
  //! Reflect a fragment if necessary through a line connecting two atoms
  /*!
 
    We want add the new fragment such that, most of its atoms fall
    on the side opposite to where the atoms already embedded are aid1
    and aid2 give the atoms that were used to align the new ring to
    the embedded atoms and we will assume that that process has
    already taken place (i.e. transformRing has been called)
 
  */
  void reflectIfNecessaryDensity(EmbeddedFrag &embFrag, unsigned int aid1,
                                 unsigned int aid2);
 
  //! Reflect a fragment if necessary based on the cis/trans specification
  /*!
 
    we want to add the new fragment such that the cis/trans
    specification on bond between aid1 and aid2 is not violated. We
    will assume that aid1 and aid2 from this fragments as well as
    embFrag are already aligned to each other.
 
    \param embFrag   the fragment that will be reflected if necessary
    \param ctCase    which fragment if the cis/trans dbl bond
                      - 1 means embFrag is the cis/trans fragment
                      - 2 mean "this" is the cis/trans fragment
    \param aid1      first atom that forms the plane (line) of reflection
    \param aid2      second atom that forms the plane of reflection
  */
  void reflectIfNecessaryCisTrans(EmbeddedFrag &embFrag, unsigned int ctCase,
                                  unsigned int aid1, unsigned int aid2);
 
  //! Reflect a fragment if necessary based on a third common point
  /*!
 
    we want add the new fragment such that the third point falls on
    the same side of aid1 and aid2. We will assume that aid1 and
    aid2 from this fragments as well as embFrag are already aligned
    to each other.
 
  */
  void reflectIfNecessaryThirdPt(EmbeddedFrag &embFrag, unsigned int aid1,
                                 unsigned int aid2, unsigned int aid3);
 
  //! \brief Initialize this fragment from a ring and coordinates for its atoms
  /*!
    ARGUMENTS:
    /param ring     a vector of atom ids in the ring; it is assumed that there
    in
                    clockwise or anti-clockwise order
    /param nringMap a map of atomId to coordinate map for the atoms in the ring
  */
  void initFromRingCoords(const RDKit::INT_VECT &ring,
                          const RDGeom::INT_POINT2D_MAP &nringMap);
 
  //! Helper function to addNonRingAtom to a specified atoms in the fragment
  /*
    Add an atom to this embedded fragment when the fragment already
    has at least two neighbors previously added to 'toAid'. In this
    case we have to choose where the new neighbor goes based on
    the angle that is already taken around the atom.
 
    ARGUMENTS:
    \param aid    ID of the atom to be added
    \param toAid  ID of the atom that is already in this object to which this
    atom is added
  */
  void addAtomToAtomWithAng(unsigned int aid, unsigned int toAid);
 
  //! Helper function to addNonRingAtom to a specified atoms in the fragment
  /*!
 
    Add an atom (aid) to an atom (toAid) in this embedded fragment
    when 'toAid' has one or no neighbors previously added. In this
    case where the new atom should fall is determined by the degree
    of 'toAid' and the congestion around it.
 
    ARGUMENTS:
    \param  aid     ID of the atom to be added
    \param  toAid   ID of the atom that is already in this object to which this
    atom is added
    \param  mol     the molecule we are dealing with
  */
  void addAtomToAtomWithNoAng(
      unsigned int aid,
      unsigned int toAid);  //, const RDKit::ROMol *mol);
 
  //! Helper function to constructor that takes predefined coordinates
  /*!
 
    Given an atom with more than 2 neighbors all embedded in this
    fragment this function tries to determine
 
    - how much of an angle if left for any new neighbors yet to be
      added
    - which atom should we rotate when we add a new neighbor and in
      which direction (clockwise or anticlockwise
 
    This is how it works
    - find the pair of nbrs that have the largest angle
    - this will most likely be the angle that is available - unless
      we have fused rings and we found on of the ring angle !!!! -
      in this case we find the next best
    - find the smallest angle that contains one of these nbrs -
      this determined which
    - way we want to rotate
 
    ARGUMENTS:
    \param aid        the atom id where we are centered right now
    \param doneNbrs   list of neighbors that are already embedded around aid
  */
  void computeNbrsAndAng(unsigned int aid, const RDKit::INT_VECT &doneNbrs);
  // const RDKit::ROMol *mol);
 
  //! are we embedded with the final (molecule) coordinates
  bool d_done = false;
  double d_px = 0.0, d_nx = 0.0, d_py = 0.0, d_ny = 0.0;
 
  //! a map that takes one from the atom id to the embeddedatom object for that
  /// atom.
  INT_EATOM_MAP d_eatoms;
 
  // RDKit::INT_DEQUE d_attachPts;
  RDKit::INT_LIST d_attachPts;
 
  // pointer to the owning molecule
  const RDKit::ROMol *dp_mol = nullptr;
};
}  // namespace RDDepict
 
#endif