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pharmarec.cpp
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pharmarec.cpp
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/*
Pharmer: Efficient and Exact 3D Pharmacophore Search
Copyright (C) 2011 David Ryan Koes and the University of Pittsburgh
This program is free software; you can redistribute it and/or
modify it under the terms of the GNU General Public License
as published by the Free Software Foundation; either version 2
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 copy of the GNU 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.
*/
/*
* pharmarec.cpp
*
* Created on: Dec 1-, 2009
* Author: dkoes
*
* Read in a file and identify all the pharma points.
* Can either use smarts or built in recognition routines.
* Can either print points to stdout or modify the file with representative atoms.
* This version uses OEChem instead of OpenBabel
*/
#include <getopt.h>
#include <iostream>
#include <cassert>
#include <string>
#include "pharmarec.h"
#include "Timer.h"
#include <boost/lexical_cast.hpp>
#include <boost/assign/list_of.hpp>
#include <boost/unordered_set.hpp>
#include <boost/algorithm/string.hpp>
#include <boost/algorithm/string/trim.hpp>
#include <boost/foreach.hpp>
using namespace boost;
using namespace OpenBabel;
cl::opt<bool> DKoesTest("dkoes", cl::Hidden);
//default pharmacophore definitions
//The original definitions are due to Lidio Meireles and have been subsequently modified by me (dkoes)
const char *aromatic[] =
{ "a1aaaaa1", "a1aaaa1", NULL };
const char * hydrogen_donor[] =
{ "[#7!H0&!$(N-[SX4](=O)(=O)[CX4](F)(F)F)]", "[#8!H0&!$([OH][C,S,P]=O)]",
"[#16!H0]", NULL };
const char * hydrogen_acceptor[] =
{ "[#7&!$([nX3])&!$([NX3]-*=[!#6])&!$([NX3]-[a])&!$([NX4])&!$(N=C([C,N])N)]",
"[$([O])&!$([OX2](C)C=O)&!$(*(~a)~a)]", NULL };
const char * positive_ion[] =
{ "[+,+2,+3,+4]",
//amidine
"[$(CC)](=N)N",
//guanidine
"[$(C(N)(N)=N)]", "[$(n1cc[nH]c1)]", NULL };
const char * negative_ion[] =
{ "[-,-2,-3,-4]", "C(=O)[O-,OH,OX1]", "[$([S,P](=O)[O-,OH,OX1])]",
"c1[nH1]nnn1", "c1nn[nH1]n1", "C(=O)N[OH1,O-,OX1]", "C(=O)N[OH1,O-]",
"CO(=N[OH1,O-])",
//trifluoromethyl sulfonamide
"[$(N-[SX4](=O)(=O)[CX4](F)(F)F)]", NULL };
const char *hydrophobic[] =
{
"a1aaaaa1",
"a1aaaa1",
//branched terminals as one point
"[$([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])&!$(**[CH3X4,CH2X3,CH1X2,F,Cl,Br,I])]",
"[$(*([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])[CH3X4,CH2X3,CH1X2,F,Cl,Br,I])&!$(*([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])[CH3X4,CH2X3,CH1X2,F,Cl,Br,I])]([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])[CH3X4,CH2X3,CH1X2,F,Cl,Br,I]",
"*([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])[CH3X4,CH2X3,CH1X2,F,Cl,Br,I]",
//simple rings only; need to combine points to get good results for 3d structures
"[C&r3]1~[C&r3]~[C&r3]1",
"[C&r4]1~[C&r4]~[C&r4]~[C&r4]1",
"[C&r5]1~[C&r5]~[C&r5]~[C&r5]~[C&r5]1",
"[C&r6]1~[C&r6]~[C&r6]~[C&r6]~[C&r6]~[C&r6]1",
"[C&r7]1~[C&r7]~[C&r7]~[C&r7]~[C&r7]~[C&r7]~[C&r7]1",
"[C&r8]1~[C&r8]~[C&r8]~[C&r8]~[C&r8]~[C&r8]~[C&r8]~[C&r8]1",
//aliphatic chains
"[CH2X4,CH1X3,CH0X2]~[CH3X4,CH2X3,CH1X2,F,Cl,Br,I]",
"[$([CH2X4,CH1X3,CH0X2]~[$([!#1]);!$([CH2X4,CH1X3,CH0X2])])]~[CH2X4,CH1X3,CH0X2]~[CH2X4,CH1X3,CH0X2]",
"[$([CH2X4,CH1X3,CH0X2]~[CH2X4,CH1X3,CH0X2]~[$([CH2X4,CH1X3,CH0X2]~[$([!#1]);!$([CH2X4,CH1X3,CH0X2])])])]~[CH2X4,CH1X3,CH0X2]~[CH2X4,CH1X3,CH0X2]~[CH2X4,CH1X3,CH0X2]",
// sulfur (apparently)
"[$([S]~[#6])&!$(S~[!#6])]", NULL };
const vector<Pharma> defaultPharmaVec = assign::list_of(
Pharma(0, "Aromatic", aromatic, 18, 1.1, 0.1))(
Pharma(1, "HydrogenDonor", hydrogen_donor, 1, .5, 0.1))(
Pharma(2, "HydrogenAcceptor", hydrogen_acceptor, 89, .5, 0.1))(
Pharma(3, "PositiveIon", positive_ion, 7, .75, 0.1))(
Pharma(4, "NegativeIon", negative_ion, 8, .75, 0.1))(
Pharma(5, "Hydrophobic", hydrophobic, 6, 1.0, 2.0));
//TODO: make this user-configurable
static unordered_map<string, PharmaInteract> pharmaInteractions =
assign::map_list_of("Aromatic", PharmaInteract(0, 5, 1))(
"HydrogenDonor", PharmaInteract(2, 4, 1))("HydrogenAcceptor",
PharmaInteract(1, 4, 1))("PositiveIon", PharmaInteract(4, 5, 1))(
"NegativeIon", PharmaInteract(3, 5, 1))("Hydrophobic",
PharmaInteract(5, 6, 3));
//reduced set of pharmacophore definitions for proteins
const char * positive_ion_protein[] =
{ "[+,+2,+3,+4]",
//amidine
//guanidine
"[$(C(N)(N)=N)]", "[$(n1cc[nH]c1)]", NULL };
const char * negative_ion_protein[] =
{ "[-,-2,-3,-4]", "C(=O)[O-,OH,OX1]", NULL };
const char *hydrophobic_protein[] =
{
"a1aaaaa1",
"a1aaaa1",
//branched terminals as one point
"[$([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])&!$(**[CH3X4,CH2X3,CH1X2,F,Cl,Br,I])]",
"[$(*([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])[CH3X4,CH2X3,CH1X2,F,Cl,Br,I])&!$(*([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])[CH3X4,CH2X3,CH1X2,F,Cl,Br,I])]([CH3X4,CH2X3,CH1X2,F,Cl,Br,I])[CH3X4,CH2X3,CH1X2,F,Cl,Br,I]",
"[CH2X4,CH1X3,CH0X2]~[CH3X4,CH2X3,CH1X2,F,Cl,Br,I]",
"[$([CH2X4,CH1X3,CH0X2]~[$([!#1]);!$([CH2X4,CH1X3,CH0X2])])]~[CH2X4,CH1X3,CH0X2]~[CH2X4,CH1X3,CH0X2]",
"[$([S]~[#6])&!$(S~[!#6])]", NULL };
static const vector<Pharma> proteinPharmaVec = assign::list_of(
Pharma(0, "Aromatic", aromatic, 18, 1.1, 0.1))(
Pharma(1, "HydrogenDonor", hydrogen_donor, 1, .5, 0.1))(
Pharma(2, "HydrogenAcceptor", hydrogen_acceptor, 89, .5, 0.1))(
Pharma(3, "PositiveIon", positive_ion_protein, 7, .75, 0.1))(
Pharma(4, "NegativeIon", negative_ion_protein, 8, .75, 0.1))(
Pharma(5, "Hydrophobic", hydrophobic_protein, 6, 1.0, 2.0));
static Pharmas proteinPharmas(proteinPharmaVec);
//setup lookup tables, pharmas must be initialized
//use a manually managed array to make sure pointers stay valid
void Pharmas::initialize(const vector<Pharma>& ps)
{
if (pharmas != NULL)
delete[] pharmas;
nameLookup.clear();
pharmas = new Pharma[ps.size()];
numPharmas = ps.size();
for (unsigned i = 0; i < numPharmas; i++)
{
pharmas[i] = ps[i];
nameLookup[pharmas[i].name] = i;
}
}
bool Pharma::operator==(const Pharma& rhs) const
{
if (name != rhs.name)
return false;
if (atomic_number_label != rhs.atomic_number_label)
return false;
if (index != rhs.index)
return false;
if (defaultSearchRadius != rhs.defaultSearchRadius)
return false;
if (getVectors != rhs.getVectors)
return false;
if (smarts.size() != rhs.smarts.size())
return false;
for (unsigned i = 0, n = smarts.size(); i < n; i++)
{
if (smarts[i].GetSMARTS() != rhs.smarts[i].GetSMARTS())
return false;
}
return true;
}
//return pharma from name
const Pharma* Pharmas::pharmaFromName(const string& name) const
{
unordered_map<string, unsigned>::const_iterator pos = nameLookup.find(name);
if (pos == nameLookup.end())
{
return NULL;
}
return &pharmas[pos->second];
}
bool Pharmas::operator==(const Pharmas& rhs) const
{
if (numPharmas != rhs.numPharmas)
return false;
for (unsigned i = 0; i < numPharmas; i++)
{
if (pharmas[i] != rhs.pharmas[i])
return false;
}
return true;
}
static void readVectors(stringstream& str, vector<vector3>& vecs)
{
while (str && ::isblank(str.peek()))
str.get();
while (str && str.peek() == '[')
{
double x, y, z;
str >> x;
str >> y;
str >> z;
vecs.push_back(vector3(x, y, z));
char c;
str >> c; //end bracket
while (str && ::isblank(str.peek()))
str.get();
}
}
//read in query pharma
bool PharmaPoint::read(const Pharmas& pharmas, istream &in)
{
string line;
getline(in, line);
stringstream str(line);
//init
size = 0;
vecpivot = 0;
requirements = Required;
radius = 0;
string name;
str >> name;
pharma = pharmas.pharmaFromName(name);
if (pharma == NULL)
return false;
int anum = 0;
str >> anum;
if (anum != pharma->atomic_number_label)
return false;
str >> x;
str >> y;
str >> z;
if (!str)
return false;
readVectors(str, vecs);
str >> radius;
char r = 0;
str >> r;
switch (r)
{
case 'r':
case 'R':
requirements = Required;
break;
case 'n':
case 'N':
requirements = NotPresent;
break;
case 'o':
case 'O':
requirements = Optional;
break;
}
str >> vecpivot;
return true;
}
//write out textual description of pharma point
ostream &operator<<(ostream &stream, const PharmaPoint& obj)
{
stream << obj.pharma->name << " ";
stream << obj.pharma->atomic_number_label << " ";
stream << obj.x << ' ' << obj.y << ' ' << obj.z;
for (unsigned i = 0, n = obj.vecs.size(); i < n; i++)
{
stream << " [ " << obj.vecs[i].x() << " " << obj.vecs[i].y() << " "
<< obj.vecs[i].z() << " ]";
}
return stream;
}
//read from a json formatted stream, return true if successfull
bool readPharmaPointsJSON(const Pharmas& pharmas, Json::Value& root,
vector<PharmaPoint>& points)
{
try
{
points.clear();
Json::Value jpoints = root["points"];
for (unsigned i = 0, n = jpoints.size(); i < n; i++)
{
Json::Value jpnt = jpoints[i];
if (jpnt.isMember("enabled") && !jpnt["enabled"].asBool())
continue;
string name = jpnt["name"].asString();
double radius = .1;
unsigned minsize = 0;
unsigned maxsize = UINT_MAX;
PharmaPoint::PointRequirements required = PharmaPoint::Required;
if (jpnt.isMember("radius"))
radius = jpnt["radius"].asDouble();
if (jpnt.isMember("requirement") && jpnt["required"].isString())
{
string req = jpnt["requirement"].asString();
algorithm::to_lower(req);
if (req == "optional")
required = PharmaPoint::Optional;
else if (req == "notpresent")
required = PharmaPoint::NotPresent;
}
if (jpnt.isMember("minsize") && !jpnt["minsize"].isNull())
{
if (jpnt["minsize"].isString())
{
if (jpnt["minsize"].asString().length() > 0)
{
try
{
minsize = lexical_cast<unsigned>(
jpnt["minsize"].asString());
} catch (std::exception& e)
{
}
}
}
else
minsize = jpnt["minsize"].asUInt();
}
if (jpnt.isMember("maxsize") && !jpnt["maxsize"].isNull())
{
if (jpnt["maxsize"].isString())
{
if (jpnt["maxsize"].asString().length() > 0)
{
try
{
maxsize = lexical_cast<unsigned>(
jpnt["maxsize"].asString());
} catch (std::exception& e)
{
}
}
}
else
maxsize = jpnt["maxsize"].asUInt();
}
double x = jpnt["x"].asDouble();
double y = jpnt["y"].asDouble();
double z = jpnt["z"].asDouble();
const Pharma* p = pharmas.pharmaFromName(name);
if (p == NULL)
continue;
unsigned size = 1;
if (jpnt.isMember("size"))
size = jpnt["size"].asUInt();
PharmaPoint pnt;
pnt.pharma = p;
pnt.x = x;
pnt.y = y;
pnt.z = z;
pnt.size = size;
pnt.maxSize = maxsize;
pnt.minSize = minsize;
if (!jpnt.isMember("vector_on") || jpnt["vector_on"].asBool())
{
if (jpnt.isMember("svector") && !jpnt["svector"].isNull())
{
pnt.vecs.push_back(
vector3(jpnt["svector"]["x"].asDouble(),
jpnt["svector"]["y"].asDouble(),
jpnt["svector"]["z"].asDouble()));
}
else if (jpnt.isMember("vector"))
{ //queries typically have only one vector
for (unsigned v = 0, nv = jpnt["vector"].size(); v < nv;
v++)
{
pnt.vecs.push_back(
vector3(jpnt["vector"][v]["x"].asDouble(),
jpnt["vector"][v]["y"].asDouble(),
jpnt["vector"][v]["z"].asDouble()));
}
}
}
pnt.radius = radius;
pnt.requirements = required;
points.push_back(pnt);
}
} catch (std::exception& e)
{
//poorly formated json
cerr << "Parse " << e.what() << "\n";
return false;
}
return true;
}
//return location of max degree, return false if no nonzero degrees
static bool findMax(vector<unsigned>& degrees, unsigned n, unsigned& maxi)
{
unsigned m = 0;
for (unsigned i = 0; i < n; i++)
{
if (degrees[i] > m)
{
m = degrees[i];
maxi = i;
}
}
return m > 0;
}
struct Coord
{
double x;
double y;
double z;
Coord(double X, double Y, double Z) :
x(X), y(Y), z(Z)
{
}
Coord() :
x(0), y(0), z(0)
{
}
bool operator==(const Coord& rhs) const
{
return x == rhs.x && y == rhs.y && z == rhs.z;
}
};
static size_t hash_value(const Coord & t)
{
size_t seed = 0;
hash_combine(seed, t.x);
hash_combine(seed, t.y);
hash_combine(seed, t.z);
return seed;
}
//sort an indexing array into points by distance to index point
class DistanceSorter
{
unsigned index;
const vector<PharmaPoint>& points;
public:
DistanceSorter(unsigned i, const vector<PharmaPoint>& pts) :
index(i), points(pts)
{
}
bool operator()(unsigned i, unsigned j) const
{
double d1 = PharmaPoint::pharmaDist(points[index], points[i]);
double d2 = PharmaPoint::pharmaDist(points[index], points[j]);
return d1 < d2;
}
};
// greedily create clusters of points that are all separated by dist
//and replace with the cluster centers
//the common cases if for all points we want to be clustered to be in a clique
//so hopefully no need for more complex algorithms
//mutates points
static void clusterPoints(const Pharma *pharma, vector<PharmaPoint>& points,
const vector<vector<Coord> >& ptatoms, double dist)
{
unsigned n = points.size();
vector<PharmaPoint> npts;
npts.reserve(n);
vector<vector<double> > distance(n, vector<double>(n, 0));
vector<unsigned> degrees(n, 0);
//compute distances and degrees (number of close neighbors)
for (unsigned i = 0; i < n; i++)
{
for (unsigned j = 0; j < i; j++)
{
double d = PharmaPoint::pharmaDist(points[i], points[j]);
distance[j][i] = distance[i][j] = d;
if (d <= dist)
{
degrees[i]++;
degrees[j]++;
}
}
}
unsigned order[n];
//add all zero degree points
for (unsigned i = 0; i < n; i++)
{
order[i] = i;
if (degrees[i] == 0)
npts.push_back(points[i]);
}
unsigned maxi = 0;
while (findMax(degrees, n, maxi))
{
vector<unsigned> cluster;
cluster.push_back(maxi);
degrees[maxi] = 0;
DistanceSorter sorter(maxi, points);
sort(order, order + n, sorter);
//add points that are within threshold of all member of the cluster
for (unsigned o = 0; o < n; o++)
{
unsigned i = order[o];
if (degrees[i] > 0)
{
unsigned j = 0;
for (unsigned csz = cluster.size(); j < csz; j++)
{
if (distance[i][cluster[j]] > dist)
break;
}
if (j == cluster.size()) //close to all current cluster members
{
degrees[i] = 0;
cluster.push_back(i);
}
}
}
//create point with average of atom coords
unordered_set<Coord> atoms;
for (unsigned i = 0, csz = cluster.size(); i < csz; i++)
{
unsigned index = cluster[i];
for (unsigned j = 0, na = ptatoms[index].size(); j < na; j++)
{
atoms.insert(ptatoms[index][j]);
}
}
PharmaPoint pt(pharma);
BOOST_FOREACH(const Coord& a, atoms)
{
pt.x += a.x;
pt.y += a.y;
pt.z += a.z;
}
pt.x /= atoms.size();
pt.y /= atoms.size();
pt.z /= atoms.size();
pt.size = atoms.size();
npts.push_back(pt);
}
points.swap(npts);
}
/* Identify the pharma points of mol and put them in points.
* Note that this is very inefficient in processing sequences of
* multi-conformer molecules.
* */
void getPharmaPoints(const Pharmas& pharmas, OBMol& mol,
vector<PharmaPoint>& points)
{
vector<vector<PharmaPoint> > pts;
points.clear();
getPharmaPointsMC(pharmas, mol, pts);
if (pts.size() > 0)
points.swap(pts[0]);
}
//return true if mol is a PharmaGist mol2 and fill in points with first model
bool isPharmaGist(const Pharmas& pharmas, const string& mol,
vector<PharmaPoint>& points)
{
if (mol.substr(0, 17) != "@<TRIPOS>MOLECULE")
return false;
istringstream str(mol);
bool readatoms = false;
string line;
while (getline(str, line))
{
if (line == "@<TRIPOS>ATOM")
readatoms = true;
else if (line == "@<TRIPOS>BOND")
return points.size() > 0;
else if (readatoms)
{
stringstream l(line);
unsigned num;
string type;
double x, y, z;
l >> num >> type >> x >> y >> z;
if(type == "DON")
{
points.push_back(PharmaPoint(x,y,z,pharmas.pharmaFromName("HydrogenDonor")));
}
else if(type == "ACC")
{
points.push_back(PharmaPoint(x,y,z,pharmas.pharmaFromName("HydrogenAcceptor")));
}
else if(type == "ANI")
{
points.push_back(PharmaPoint(x,y,z,pharmas.pharmaFromName("NegativeIon")));
}
else if(type == "CAT")
{
points.push_back(PharmaPoint(x,y,z,pharmas.pharmaFromName("PositiveIon")));
}
else if(type == "HYD")
{
points.push_back(PharmaPoint(x,y,z,pharmas.pharmaFromName("Hydrophobic")));
}
else if(type == "AR")
{
points.push_back(PharmaPoint(x,y,z,pharmas.pharmaFromName("Aromatic")));
}
else
{
points.clear();
return false;
}
}
}
points.clear();
return false;
}
void getPharmaPointsMC(const Pharmas& pharmas, OBMol& mol,
vector<vector<PharmaPoint> >& points)
{
points.clear();
points.resize(mol.NumConformers());
//for each kind of pharma
for (int p = 0, np = pharmas.size(); p < np; p++)
{
const Pharma* pharma = pharmas[p];
vector<vector<PharmaPoint> > cpoints(mol.NumConformers());
vector<vector<vector<Coord> > > ccoords(mol.NumConformers());
//foreach smart for the pharma
for (int s = 0, ns = pharma->smarts.size(); s < ns; s++)
{
const OBSmartsPattern& matcher = pharma->smarts[s];
vector<vector<int> > maplist;
if (matcher.Match(mol, maplist, OBSmartsPattern::AllUnique))
{
for (unsigned c = 0, nc = mol.NumConformers(); c < nc; c++)
{
//foreach map, record the point as the average of the matched atoms
for (int i = 0, n = maplist.size(); i < n; i++)
{
mol.SetConformer(c);
ccoords[c].resize(ccoords[c].size() + 1);
PharmaPoint point(pharma);
point.x = point.y = point.z = 0;
//get each atom
int numatoms = maplist[i].size();
point.size = numatoms;
for (int a = 0; a < numatoms; a++)
{
OBAtom *atom = mol.GetAtom(maplist[i][a]);
point.x += atom->x();
point.y += atom->y();
point.z += atom->z();
if (pharma->clusterLimit > 0)
ccoords[c].back().push_back(
Coord(atom->x(), atom->y(), atom->z()));
}
//take average
if (numatoms > 0)
{
point.x /= numatoms;
point.y /= numatoms;
point.z /= numatoms;
}
if (pharma->getVectors != NULL)
pharma->getVectors(maplist[i], mol, point);
cpoints[c].push_back(point);
}
}
}
}
//now add all points for each conformation, clustering as necessary
for (unsigned c = 0, nc = cpoints.size(); c < nc; c++)
{
if (pharma->clusterLimit > 0)
{
clusterPoints(pharma, cpoints[c], ccoords[c],
pharma->clusterLimit);
}
//add (possibly clustered) conformer points
points[c].insert(points[c].end(), cpoints[c].begin(),
cpoints[c].end());
}
}
}
/* add the passed pharma points to the molecule model */
void addPharmaPoints(OBMol& mol, vector<PharmaPoint>& points)
{
for (int p = 0, np = points.size(); p < np; p++)
{
OBAtom atom;
atom.SetVector(points[p].x, points[p].y, points[p].z);
atom.SetAtomicNum(points[p].pharma->atomic_number_label);
mol.AddAtom(atom);
}
}
//convert from vector version to json version
bool convertPharmaJson(Json::Value& root, const vector<PharmaPoint>& points)
{
//add all points
for (unsigned i = 0, n = points.size(); i < n; i++)
{
Json::Value& pt = root["points"][i];
pt["name"] = points[i].pharma->name;
pt["x"] = points[i].x;
pt["y"] = points[i].y;
pt["z"] = points[i].z;
pt["size"] = points[i].size;
for (unsigned j = 0, nv = points[i].vecs.size(); j < nv; j++)
{
pt["vector"][j]["x"] = points[i].vecs[j].x();
pt["vector"][j]["y"] = points[i].vecs[j].y();
pt["vector"][j]["z"] = points[i].vecs[j].z();
}
pt["radius"] = points[i].radius;
pt["requirement"] = points[i].requirementStr();
}
return true;
}
//look for hydrogens bonded to first atom, take bond to H as vector
static void genHDonorPointVector(const vector<int>& atom_indexes,
const OBMol& mol, PharmaPoint& pnt)
{
if (atom_indexes.size() == 0)
{
return;
}
OBAtom *atom = mol.GetAtom(atom_indexes[0]);
OBBondIterator i;
for (OBAtom* nbor = atom->BeginNbrAtom(i); nbor;
nbor = atom->NextNbrAtom(i))
{
if (nbor->GetAtomicNum() == 1)
{
vector3 vec1 = atom->GetVector();
vector3 vec2 = nbor->GetVector();
vector3 vec = vec2 - vec1;
if (!isfinite(vec.x()))
continue; //sometimes, despite our best efforts, H has same coords as N
vec.normalize();
pnt.vecs.push_back(vec);
}
}
}
//acceptors are trickier.. if a hydrogen exists, use that direction,
//otherwise use opposite of average of existing bonds
static void genHAcceptorPointVector(const vector<int>& atom_indexes,
const OBMol& mol, PharmaPoint& pnt)
{
if (atom_indexes.size() == 0)
{
return;
}
OBAtom *atom = mol.GetAtom(atom_indexes[0]);
OBBondIterator i;
bool foundvec = false;
for (OBAtom* nbor = atom->BeginNbrAtom(i); nbor;
nbor = atom->NextNbrAtom(i))
{
if (nbor->GetAtomicNum() == 1)
{
vector3 vec1;
vector3 vec2;
vec1 = atom->GetVector();
vec2 = nbor->GetVector();
vector3 vec = vec2 - vec1;
if (!isfinite(vec.x()))
continue; //sometimes, despite our best efforts, H has same coords as N
vec.normalize();
pnt.vecs.push_back(vec);
foundvec = true;
}
}
if (!foundvec)
{
vector3 avebond(0, 0, 0);
vector3 avec = atom->GetVector();
unsigned cnt = 0;
OBBondIterator i;
for (OBAtom* nbor = atom->BeginNbrAtom(i); nbor;
nbor = atom->NextNbrAtom(i))
{
avebond += nbor->GetVector() - avec;
cnt++;
}
avebond /= cnt;
avebond *= -1;
avebond.normalize();
if(isfinite(avebond.x()))
pnt.vecs.push_back(avebond);
}
}
//just pick some normal to the ring
static void genAromaticPointVector(const vector<int>& atom_indexes,
const OBMol& mol, PharmaPoint& pnt)
{
if (atom_indexes.size() < 3)
{
return;
}
vector3 base = mol.GetAtom(atom_indexes[0])->GetVector();
vector3 pt1 = mol.GetAtom(atom_indexes[1])->GetVector();
vector3 pt2 = mol.GetAtom(atom_indexes[2])->GetVector();
vector3 norm = cross((pt2 - base), (pt1 - base));
norm.normalize();
pnt.vecs.push_back(norm);
pnt.vecs.push_back(-norm);
}
void Pharma::setVectorFn(genPointVectorFn fn)
{
if (fn != NULL)
{
getVectors = fn;
}
else
{
if (boost::starts_with(name, "Aromatic"))
getVectors = genAromaticPointVector;
else if (boost::starts_with(name,"HydrogenDonor"))
getVectors = genHDonorPointVector;
else if (boost::starts_with(name, "HydrogenAcceptor"))
getVectors = genHAcceptorPointVector;
else
getVectors = NULL;
}
}
//write out pharma definitions
void Pharmas::write(ostream& out) const
{
for (unsigned i = 0; i < numPharmas; i++)
{
out << pharmas[i].name << " ";
out << pharmas[i].atomic_number_label << " ";
assert(i == pharmas[i].index);
out << i << " ";
out << pharmas[i].defaultSearchRadius << " ";
//0, no vectors
//1, default
//anything else has to be done programatically
if (pharmas[i].getVectors != NULL)
out << "1 ";
else
out << "0 ";
out << pharmas[i].clusterLimit << " ";
out << "\n";
//now list all smarts
for (unsigned s = 0, ns = pharmas[i].smarts.size(); s < ns; s++)
{
out << pharmas[i].smarts[s].GetSMARTS() << "\n";
}
//blank line between pharmas
out << "\n";
}
}
//read in pharma definitions
bool Pharmas::read(istream& in)
{
string line;
vector<Pharma> pharmavec;
while (getline(in, line))
{
//first line has all info
Pharma p;
stringstream str(line);
str >> p.name;
str >> p.atomic_number_label;
str >> p.index;
if (p.index != pharmavec.size())
p.index = pharmavec.size(); //making this explicit was really stupid, just use order from file
str >> p.defaultSearchRadius;
int vecid = 0;
str >> vecid;
if (vecid == 1)
p.setVectorFn();
else if (vecid > 1)
return false; //unknown vector generator
str >> p.clusterLimit;
if (!str) //fail bit got set
return false;
//now read in smarts
while (getline(in, line))
{
if (line.length() == 0)
break; //empty line
p.smarts.push_back(OBSmartsPattern());
p.smarts.back().Init(line);
}
if (p.smarts.size() == 0)
return false;
pharmavec.push_back(p);
}
initialize(pharmavec);
return true;
}
//output a set of points in json format that is suitable for query based on
//the data in moldata
bool jsonPharmaQuery(const Pharmas& pharmas, Json::Value& root,
const string& moldata, OBFormat *format, const string& recdata,
OBFormat *rformat)
{
vector<PharmaPoint> points;
vector<PharmaPoint> disabled;
if (isPharmaGist(pharmas, moldata, points))
; //got points from the file
else
{
OBMol mol;
OBConversion conv;
conv.SetInFormat(format);
if (!conv.ReadString(&mol, moldata))
return false;
if (rformat == NULL || recdata.length() == 0)
{
getPharmaPoints(pharmas, mol, points);
}
else //compute interaction pharma
{
conv.SetInFormat(rformat);
OBMol rec;