1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
|
//
// Copyright (C) David Cosgrove 2024.
//
// @@ 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 <algorithm>
#include <chrono>
#include <filesystem>
#include <fstream>
#include <GraphMol/SubstructLibrary/SubstructLibrary.h>
#include <GraphMol/FileParsers/MolSupplier.h>
#include <GraphMol/Fingerprints/MorganGenerator.h>
#include <GraphMol/Fingerprints/RDKitFPGenerator.h>
#include <GraphMol/SynthonSpaceSearch/SynthonSpace.h>
#include <GraphMol/SynthonSpaceSearch/SearchResults.h>
#include <GraphMol/SynthonSpaceSearch/SynthonSpaceSearch_details.h>
#include <GraphMol/SmilesParse/SmilesParse.h>
#include <GraphMol/SmilesParse/SmilesWrite.h>
#include <catch2/catch_all.hpp>
using namespace RDKit;
using namespace RDKit::SynthonSpaceSearch;
using namespace RDKit::SynthonSpaceSearch::details;
const char *rdbase = getenv("RDBASE");
std::map<std::string, std::unique_ptr<ExplicitBitVect>> getFingerprints(
const std::string &molFilename,
std::map<std::string, std::unique_ptr<RWMol>> &mols,
const std::unique_ptr<FingerprintGenerator<std::uint64_t>> &fpGen) {
v2::FileParsers::SmilesMolSupplierParams fileparams;
fileparams.titleLine = false;
v2::FileParsers::SmilesMolSupplier suppl(molFilename, fileparams);
std::map<std::string, std::unique_ptr<ExplicitBitVect>> fps;
while (!suppl.atEnd()) {
auto mol = suppl.next();
auto fp = fpGen->getFingerprint(*mol);
fps.insert(std::make_pair(
mol->getProp<std::string>(common_properties::_Name), fp));
auto molName = mol->getProp<std::string>(common_properties::_Name);
mols.insert(std::make_pair(molName, mol.release()));
}
return fps;
}
std::set<std::string> bruteForceSearch(
std::map<std::string, std::unique_ptr<ExplicitBitVect>> &fps,
const ROMol &queryMol, const double simCutoff) {
std::unique_ptr<FingerprintGenerator<std::uint64_t>> fpGen;
fpGen.reset(MorganFingerprint::getMorganGenerator<std::uint64_t>(2));
const auto queryFP =
std::unique_ptr<ExplicitBitVect>(fpGen->getFingerprint(queryMol));
std::set<std::string> fullSmi;
std::set<std::string> names;
for (auto &it : fps) {
if (auto sim = TanimotoSimilarity(*it.second, *queryFP); sim >= simCutoff) {
names.insert(it.first);
}
}
return names;
}
TEST_CASE("FP Small tests") {
REQUIRE(rdbase);
std::string fName(rdbase);
std::string fullRoot(fName + "/Code/GraphMol/SynthonSpaceSearch/data/");
std::vector<std::string> libNames{
fullRoot + "amide_space.txt",
fullRoot + "triazole_space.txt",
fullRoot + "urea_space.txt",
};
std::vector<std::string> enumLibNames{
fullRoot + "amide_space_enum.smi",
fullRoot + "triazole_space_enum.smi",
fullRoot + "urea_space_enum.smi",
};
std::vector<std::string> querySmis{
"c1ccccc1C(=O)N1CCCC1",
"CC1CCN(c2nnc(CO)n2C2CCCC2)C1",
"C[C@@H]1CC(NC(=O)NC2COC2)CN(C(=O)c2nccnc2F)C1",
};
std::vector<size_t> expNumHits{2, 3, 4};
for (size_t i = 0; i < libNames.size(); i++) {
SynthonSpace synthonspace;
bool cancelled = false;
synthonspace.readTextFile(libNames[i], cancelled);
SynthonSpaceSearchParams params;
params.randomSeed = 1;
params.approxSimilarityAdjuster = 0.2;
auto queryMol = v2::SmilesParse::MolFromSmiles(querySmis[i]);
std::unique_ptr<FingerprintGenerator<std::uint64_t>> fpGen(
MorganFingerprint::getMorganGenerator<std::uint64_t>(2));
auto results = synthonspace.fingerprintSearch(*queryMol, *fpGen, params);
CHECK(results.getHitMolecules().size() == expNumHits[i]);
std::set<std::string> resSmis;
for (const auto &r : results.getHitMolecules()) {
resSmis.insert(MolToSmiles(*r));
}
// Do the enumerated library, just to check
std::map<std::string, std::unique_ptr<RWMol>> mols;
auto fps = getFingerprints(enumLibNames[i], mols, fpGen);
auto names = bruteForceSearch(fps, *queryMol, params.similarityCutoff);
std::set<std::string> fullSmis;
for (const auto &r : names) {
fullSmis.insert(MolToSmiles(*mols[r]));
}
if (i != 1) {
CHECK(resSmis == fullSmis);
} else {
// In the triazole library, one of the hits found by the brute force
// method (triazole-1_1-1_2-2_3-1) is missed by the SynthonSpaceSearch
// because it requires that the fragment [1*]n([3*])C1CCCC1 is similar
// to synthon c1ccccc1-n([3*])[1*] which it isn't. Instead, make sure
// all the ones that are found are in the brute force results.
for (const auto &rs : resSmis) {
CHECK(fullSmis.find(rs) != fullSmis.end());
}
}
}
}
TEST_CASE("FP Binary File") {
REQUIRE(rdbase);
std::string fName(rdbase);
SynthonSpace synthonspace;
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/idorsia_toy_space_a.spc";
std::unique_ptr<FingerprintGenerator<std::uint64_t>> fpGen(
RDKitFP::getRDKitFPGenerator<std::uint64_t>());
SearchResults results;
auto queryMol = "O=C(Nc1c(CNC=O)cc[s]1)c1nccnc1"_smiles;
SynthonSpaceSearchParams params;
for (auto numThreads : std::vector<int>{1, 2, -1}) {
synthonspace.readDBFile(libName, numThreads);
params.numThreads = numThreads;
CHECK_NOTHROW(
results = synthonspace.fingerprintSearch(*queryMol, *fpGen, params));
CHECK(results.getHitMolecules().size() == 4);
CHECK(results.getMaxNumResults() == 420);
}
// Make sure it rejects the wrong sort of fingerprint.
synthonspace.readDBFile(libName);
fpGen.reset(MorganFingerprint::getMorganGenerator<std::uint64_t>(2));
CHECK_THROWS(results = synthonspace.fingerprintSearch(*queryMol, *fpGen));
}
TEST_CASE("Missing exact match") {
REQUIRE(rdbase);
std::string fName(rdbase);
SynthonSpace synthonspace;
std::string libName =
fName + "/Code/GraphMol/SynthonSpaceSearch/data/missing_hit.txt";
std::unique_ptr<FingerprintGenerator<std::uint64_t>> fpGen(
RDKitFP::getRDKitFPGenerator<std::uint64_t>());
SearchResults results;
auto queryMol =
"N#Cc1ccc(C(=O)Cn2cc(-c3cn[nH]c3-c3nc4ccccc4[nH]3)nn2)s1"_smiles;
bool cancelled = false;
synthonspace.readTextFile(libName, cancelled);
synthonspace.buildSynthonFingerprints(*fpGen);
CHECK_NOTHROW(results = synthonspace.fingerprintSearch(*queryMol, *fpGen));
CHECK(results.getHitMolecules().size() == 1);
CHECK(results.getHitMolecules()[0]->getProp<double>("Similarity") == 1.0);
}
|
