/*
* Copyright (c) 1997 - 2016
* Actelion Pharmaceuticals Ltd.
* Gewerbestrasse 16
* CH-4123 Allschwil, Switzerland
*
* All rights reserved.
*
* Redistribution and use in source and binary forms, with or without
* modification, are permitted provided that the following conditions are met:
*
* 1. Redistributions of source code must retain the above copyright notice, this
* list of conditions and the following disclaimer.
* 2. Redistributions in binary form must reproduce the above copyright notice,
* this list of conditions and the following disclaimer in the documentation
* and/or other materials provided with the distribution.
* 3. Neither the name of the the copyright holder nor the
* names of its contributors may be used to endorse or promote products
* derived from this software without specific prior written permission.
*
* THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS" AND
* ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED
* WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE
* DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT OWNER OR CONTRIBUTORS BE LIABLE FOR
* ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES
* (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES;
* LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND
* ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT
* (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS
* SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
*
*/
package com.actelion.research.chem.prediction;
import com.actelion.research.chem.*;
import com.actelion.research.util.DoubleFormat;
import com.actelion.research.util.SortedList;
import java.text.DecimalFormat;
import java.text.NumberFormat;
import java.util.ArrayList;
import java.util.Arrays;
import java.util.TreeMap;
public class CLogPPredictor {
private static final int ATOM_TYPE_MODE = AtomTypeCalculator.cPropertiesForCLogPCharges;
protected static final long[] ATOM_TYPE = {
0x80002L, 0x80004L, 0x90002L, 0x90003L,
0x90004L, 0x90005L, 0x90008L, 0x90009L,
0x9000dL, 0x9000eL, 0x92003L, 0x92004L,
0x92008L, 0x94003L, 0xa8002L, 0xa8003L,
0xa8004L, 0xa8009L, 0xa800eL, 0xaa004L,
0xc8002L, 0xc8003L, 0xc8004L, 0xc8005L,
0xc800eL, 0xca004L, 0x100004L, 0x110002L,
0x110003L, 0x110004L, 0x110008L, 0x128004L,
0x12a003L, 0x148004L, 0x148008L, 0x190002L,
0x190003L, 0x1090002L, 0x1090003L, 0x1090004L,
0x1090005L, 0x1090008L, 0x1090009L, 0x109000dL,
0x109000eL, 0x1092004L, 0x10a8002L, 0x10a8004L,
0x10a8009L, 0x10aa004L, 0x48080002L, 0x48080008L,
0x48080048L, 0x48090002L, 0x48090003L, 0x48090004L,
0x48090008L, 0x4809000cL, 0x48090042L, 0x48090043L,
0x48090044L, 0x48090048L, 0x48092003L, 0x48094003L,
0x48094043L, 0x54090002L, 0x54090003L, 0x54090004L,
0x54090008L, 0x54090042L, 0x54090043L, 0x54090044L,
0x54090048L, 0x54092003L, 0x540a8002L, 0x540a8008L,
0x540a8042L, 0x64080004L, 0x64090002L, 0x64090003L,
0x64090004L, 0x64090008L, 0x64090042L, 0x64090043L,
0x64090044L, 0x64090048L, 0x640a8002L, 0x640a8003L,
0x640a8004L, 0x640a8042L, 0x640c8002L, 0x640c8008L,
0x640c800aL, 0x640c8042L, 0x88090002L, 0x88090003L,
0x88090042L, 0x88090043L, 0x880a8002L, 0x880a8003L,
0x880a8042L, 0x880a8043L, 0x880a8044L, 0x880c8002L,
0x880c8003L, 0x880c8042L, 0x880c8043L, 0x880cc043L,
0x94090002L, 0x94090003L, 0x94090042L, 0x94090043L,
0x94090044L, 0x94090048L, 0x940a8002L, 0x940a8003L,
0x940a8042L, 0x940a8043L, 0x94112003L, 0x9412a003L,
0xa4128002L, 0xc8090002L, 0xc80aa003L, 0xd4090002L,
0xd40a8002L, 0xd40c8002L, 0x809010042L, 0x809010043L,
0x809010044L, 0x809010048L, 0x809012043L, 0x809014043L,
0x815010042L, 0x815010043L, 0x815010044L, 0x815010048L,
0x815028042L, 0x815028043L, 0x815028044L, 0x815028048L,
0x825010042L, 0x825010043L, 0x825028042L, 0x825028043L,
0x825028044L, 0x848090002L, 0x848090003L, 0x848090004L,
0x848090008L, 0x84809000cL, 0x848090042L, 0x848090043L,
0x848090044L, 0x848090048L, 0x84809004cL, 0x8480a8002L,
0x8480a8003L, 0x8480a8004L, 0x8480a8042L, 0x8480a8048L,
0x8480c8002L, 0x8480c8003L, 0x8480c8004L, 0x8480c8008L,
0x8480c8042L, 0x8480c8043L, 0x8480c8044L, 0x8480c8048L,
0x848110002L, 0x848110003L, 0x848110042L, 0x848110043L,
0x848128002L, 0x848128003L, 0x848128043L, 0x848190002L,
0x8481a8002L, 0x849090002L, 0x849090003L, 0x849090004L,
0x849090008L, 0x849090042L, 0x849090043L, 0x849090044L,
0x849090048L, 0x854090002L, 0x854090004L, 0x854090042L,
0x8540a8002L, 0x854110002L, 0x854128002L, 0x855090002L,
0x855090003L, 0x24048080043L, 0x24048090002L, 0x24048090003L,
0x24048090042L, 0x24048090043L, 0x24048092003L, 0x24048092043L,
0x24048094003L, 0x24048094043L, 0x2a048090002L, 0x2a048090003L,
0x2a048090042L, 0x2a048090043L, 0x2a054090002L, 0x2a054090003L,
0x2a054090042L, 0x2a0540a8002L, 0x2a0540a8042L, 0x32048090002L,
0x32048090003L, 0x32048090042L, 0x32048090043L, 0x32054090002L,
0x32054090003L, 0x32054090042L, 0x320540a8002L, 0x32064090002L,
0x320640c8002L, 0x44048090002L, 0x44048090042L, 0x44048090043L,
0x44048092003L, 0x44054090002L, 0x44054090042L, 0x44054090043L,
0x44054092003L, 0x44054092043L, 0x440540a8002L, 0x440540a8042L,
0x44064090002L, 0x44064090042L, 0x440640a8042L, 0x440640c8002L,
0x440640c8042L, 0x4a048090002L, 0x4a048090008L, 0x4a048090042L,
0x4a048090043L, 0x4a048090048L, 0x4a054090002L, 0x4a054090042L,
0x4a054092003L, 0x4a0540a8002L, 0x4a0540a8007L, 0x4a0540a8042L,
0x4a0540a8048L, 0x4a0540aa003L, 0x4a064090002L, 0x4a064090042L,
0x4a0640a8002L, 0x4a0640a8042L, 0x4a0640c8042L, 0x52048090042L,
0x52054090002L, 0x52054090042L, 0x520540a8002L, 0x520540a8042L,
0x52064090042L, 0x520640a8002L, 0x520640a8042L, 0x404808090042L,
0x404808090043L, 0x404808092043L, 0x4048080a8042L, 0x4048080a8043L,
0x4048080aa043L, 0x4048080c8042L, 0x404809010042L, 0x404809010043L,
0x40a808090042L, 0x40a808090043L, 0x40a808092043L, 0x40a8080a8042L,
0x40a8080a8043L, 0x40a8080aa043L, 0x40a8080c8042L, 0x40a809010042L,
0x40a809010043L, 0x40a814090042L, 0x40a814090043L, 0x40a8140a8042L,
0x40a8140c8042L, 0x40a815010042L, 0x40a815010048L, 0x40a815028042L,
0x412808090042L, 0x4128080a8042L, 0x4128080c8042L, 0x412809010042L,
0x412814090042L, 0x4128140a8042L, 0x4128140c8042L, 0x412815010042L,
0x412825010042L, 0x424048090002L, 0x424048090003L, 0x424048090042L,
0x424048090043L, 0x424054090002L, 0x424054090003L, 0x424054090042L,
0x424054090043L, 0x4240540a8002L, 0x4240540a8042L, 0x424064090002L,
0x424064090003L, 0x424064090042L, 0x424064090043L, 0x4240640a8003L,
0x4240640a8042L, 0x4240640c8003L, 0x424088090002L, 0x424088090042L,
0x4240880a8002L, 0x4240880a8042L, 0x4240880aa003L, 0x4240880c8002L,
0x4240880c8008L, 0x4240880c8042L, 0x424094090002L, 0x424094090008L,
0x424094090042L, 0x424094090043L, 0x424094090048L, 0x4240940a8002L,
0x4240940a8008L, 0x4240940a8042L, 0x4240940aa003L, 0x4240940c8002L,
0x4240940c8042L, 0x4240a40a8002L, 0x4240a40a8042L, 0x424809010042L,
0x424809010043L, 0x424815010042L, 0x424815010043L, 0x424815012043L,
0x424815028042L, 0x424815028043L, 0x424825010042L, 0x424825028042L,
0x424848090002L, 0x424848090003L, 0x424848090042L, 0x424848090043L,
0x4248480a8002L, 0x4248480a8042L, 0x424848110002L, 0x424848110042L,
0x424848128002L, 0x424848128008L, 0x424848128042L, 0x424849090002L,
0x42a048090002L, 0x42a048090042L, 0x42a054090002L, 0x42a054090042L,
0x42a064090042L, 0x42a094090002L, 0x42a0940a8002L, 0x42a0a40a8002L,
0x42a809010042L, 0x42a815010042L, 0x42a815028042L, 0x42a848090002L,
0x42a848110042L, 0x42a848128002L, 0x42a849090002L, 0x12024048080043L,
0x12024048090001L, 0x12024048090002L, 0x12024048090042L, 0x12024048092003L,
0x12024048092043L, 0x15024048090002L, 0x15024048090042L, 0x15024048092003L,
0x15024048092043L, 0x1502a048090002L, 0x1502a048090042L, 0x1502a054090002L,
0x1502a054090042L, 0x1502a0540a8002L, 0x19024048090002L, 0x19024048090003L,
0x19024048090042L, 0x19024048090043L, 0x1902a048090002L, 0x1902a054090002L,
0x1902a0540a8002L, 0x19032048090002L, 0x19032048090042L, 0x19032054090002L,
0x19032064090002L, 0x190320640a8002L, 0x190320640c8002L, 0x22032048090003L,
0x2502a048090007L, 0x2502a054090007L, 0x2502a0540a8007L, 0x2502a0540a8047L,
0x25032054090007L, 0x250320540a8007L, 0x250320640a8007L, 0x250320640a804aL,
0x2504a048090008L, 0x2504a048090048L, 0x2504a054090008L, 0x2504a0540a8008L,
0x2504a0540a8048L, 0x2902a054090007L, 0x2902a0540a8007L, 0x290320540a8007L,
0x202404064090043L, 0x212024048090002L, 0x212024048090042L, 0x212024048092003L,
0x21202a048090002L, 0x21202a048090042L, 0x21202a054090002L, 0x21202a054090042L,
0x21202a0540a8002L, 0x2120320640c8002L, 0x21204a0540a8007L, 0x21204a094090008L,
0x21204a094090048L, 0x21204a0940a8008L, 0x21204a0940a8048L, 0x2120520540a8007L,
0x212424048090002L, 0x212424048090042L, 0x212424054090002L, 0x212424054090042L,
0x212424094128008L, 0x212424094128048L, 0x2124248480a8002L, 0x2124248480a8042L,
0x215024048090002L, 0x215024048090042L };
protected static final float[] INCREMENT = {
0.6967f, 0.0f, 0.4886f, -0.4727f, -0.0749f, 0.6262f, 0.2735f, 0.57f,
0.701f, 0.9534f, -3.6435f, -2.1509f, 0.4975f, -2.1995f, -0.2809f, -0.826f,
-0.1785f, -1.6203f, -1.096f, -0.362f, 0.1395f, -0.2975f, -1.2908f, 1.0162f,
-1.3825f, -2.5384f, 0.3317f, 0.4292f, -0.5824f, -0.1834f, 0.1306f, -0.5015f,
0.6262f, -0.5258f, 0.4244f, -0.161f, -0.2778f, 0.5111f, -0.4357f, -0.1041f,
0.3424f, -0.0615f, 0.6035f, 0.7227f, 0.4346f, -1.6821f, -0.331f, -0.498f,
-1.4915f, -0.3651f, 0.4597f, 0.3384f, 0.6633f, 0.4544f, 0.1597f, 0.6339f,
0.3504f, 0.0449f, 0.342f, 0.2611f, 0.4046f, 0.5219f, -1.065f, -1.2314f,
-1.8023f, -0.3632f, -0.4108f, 0.3057f, -0.1456f, -0.2713f, -0.5193f, 0.4526f,
0.5539f, 0.8374f, -0.707f, -0.4881f, -0.41f, 0.0f, 0.1479f, 0.3448f,
0.4298f, 0.5579f, -0.1265f, -0.0425f, 0.0767f, 0.6635f, -0.3812f, -0.8368f,
1.0287f, -0.1021f, 0.3587f, -0.5945f, 0.1692f, -0.1218f, 0.3283f, 0.2239f,
0.2043f, 0.059f, -0.4835f, 0.6165f, -0.4011f, 0.5578f, -0.2164f, -0.0175f,
0.2981f, 0.11f, 0.2715f, -0.2995f, -0.467f, 0.1566f, 0.0468f, -0.1321f,
1.3686f, 0.0f, -0.4116f, 1.0186f, -0.3935f, 0.5223f, 0.3685f, 0.2577f,
1.5193f, 0.2705f, 0.3791f, 0.012f, -0.3397f, 0.1483f, 0.2766f, 0.3593f,
0.7715f, 0.315f, -1.6185f, 0.1889f, -0.2652f, -0.0965f, 0.4202f, 0.1871f,
-0.3684f, -0.0778f, 0.8943f, 0.3694f, 0.2879f, 0.4489f, -0.2601f, 0.4771f,
0.1923f, 0.4381f, 0.1695f, 0.4525f, 0.3352f, 0.1583f, 0.4036f, -0.048f,
0.5023f, -0.2649f, 0.7691f, -0.3552f, 1.0301f, -0.1141f, -0.5932f, 0.1749f,
0.1313f, -0.1804f, 0.3994f, 0.2291f, 0.3169f, 0.3599f, -0.0039f, -0.2956f,
0.4409f, -0.1609f, 0.3775f, -0.1346f, 0.2839f, 0.5129f, 0.1266f, 0.4294f,
0.2806f, 0.4907f, 0.354f, 0.2192f, 0.1565f, 0.6935f, 0.3618f, 0.6735f,
0.5778f, -0.5636f, 0.5569f, 0.3038f, -0.3276f, -0.6992f, 0.0103f, -0.4659f,
0.3818f, 0.3317f, 0.1841f, 0.7071f, 0.1227f, 0.7949f, -0.6592f, -1.3148f,
-0.4067f, -0.1316f, -0.4925f, -0.0929f, -0.4352f, -0.2207f, -0.996f, -0.7238f,
-0.5469f, -1.2939f, -0.0136f, 0.0657f, 0.7189f, 0.057f, 0.6619f, -0.6381f,
-0.8073f, 0.2355f, 0.3048f, -0.0199f, -0.0752f, 0.4461f, 0.1559f, 1.1168f,
-1.8039f, 0.2365f, -0.2206f, 0.448f, -1.134f, -0.5653f, -0.4053f, -0.1361f,
0.2199f, 0.0536f, -0.021f, 0.6985f, 0.9643f, -0.4152f, -1.0369f, -0.183f,
0.5883f, -0.2918f, -0.5294f, -0.6541f, 0.9473f, -0.1906f, -0.8484f, -0.3457f,
0.9541f, 1.4231f, -0.7924f, -0.602f, 0.08f, -0.2596f, 0.8382f, -0.4416f,
-0.3704f, -0.7487f, -0.1079f, -0.2992f, -0.3277f, 0.0251f, -0.9188f, 0.1094f,
0.8231f, -3.2333f, 0.035f, 0.3818f, -0.738f, 0.2791f, 0.3206f, 0.5662f,
-0.3784f, 0.4032f, -1.7948f, -0.1554f, 0.3785f, 0.0534f, -0.1653f, -0.0987f,
-0.1005f, -0.6461f, 0.8035f, -0.2405f, -0.1238f, -0.3576f, 0.0961f, -0.6401f,
0.2029f, 0.2359f, 0.4951f, 0.1921f, -0.3745f, 0.3463f, 0.2899f, -0.1533f,
-0.417f, 0.377f, 0.6998f, 0.594f, 0.5912f, -0.5571f, 0.0238f, -0.2475f,
0.0307f, -0.3875f, -0.7437f, 0.5144f, 0.0057f, 0.7655f, 0.172f, -2.5624f,
-0.3066f, 0.3647f, 0.1727f, -0.0329f, -0.1893f, 0.0702f, -1.2454f, 0.1496f,
-1.3825f, 0.4146f, -0.2668f, -0.1106f, 0.0362f, -0.3189f, -0.7278f, -0.0894f,
-0.2277f, -0.2394f, 1.0112f, -0.2962f, 0.7776f, 0.2945f, -0.2234f, 0.2764f,
0.8011f, -0.1744f, 0.1581f, -1.7552f, -0.3848f, 0.5993f, 0.5268f, -0.0417f,
0.4733f, -0.3401f, -0.145f, 0.7088f, -0.1318f, 0.0426f, -0.5028f, 0.3832f,
-0.0118f, -0.4358f, 0.3749f, -0.1203f, -0.5648f, -0.1972f, -0.8769f, -0.3675f,
-0.2004f, -0.607f, -0.1857f, 0.3468f, -0.3624f, 0.5358f, -0.3701f, 0.1336f,
0.9545f, 0.1139f, -0.1699f, 0.3317f, 0.2891f, 0.2613f, -0.0344f, -1.9498f,
-2.0249f, -0.6005f, -0.6258f, -1.2349f, 0.328f, -0.5434f, -0.7712f, -0.9057f,
-0.1668f, -0.9905f, -0.0372f, -1.1638f, 0.1262f, -0.5248f, -0.1538f, -0.3682f,
0.3249f, 0.065f, 0.0511f, -0.4607f, 0.2231f, 0.2822f, 0.1397f, -0.4938f,
0.3948f, -0.4075f, -0.6411f, -0.0091f, -0.1333f, -0.5192f, -0.1661f, 0.3317f,
-0.0707f, 0.4806f, 0.3828f, 0.2229f, 0.616f, 0.3371f, 0.1884f, 0.1381f,
-1.4915f, 0.2833f, -0.1226f, -3.9189f, -0.4592f, -0.3435f, -0.6654f, -0.5056f,
-0.8631f, 0.1536f, -0.6427f, -0.0884f, -0.0471f, 0.1106f, 0.3821f, -0.2392f,
-0.4051f, 0.0891f, -0.6972f, -0.4699f, 0.0922f, 0.0806f, -0.6774f, -0.0622f,
-0.93f, 0.1337f };
public static final float cCLogPUnknown = -999f;
private static SortedList<Long> sSortedTypeList;
public CLogPPredictor() {
if (sSortedTypeList == null) {
synchronized(CLogPPredictor.class) {
if (sSortedTypeList == null) {
sSortedTypeList = new SortedList<Long>();
for (Long l:ATOM_TYPE)
sSortedTypeList.add(l);
}
}
}
}
/**
* Ambiguous bonds are normalized.
* @param mol
* @return
*/
public float assessCLogP(StereoMolecule mol) {
float cLogP = 0.0f;
mol.normalizeAmbiguousBonds();
mol.ensureHelperArrays(Molecule.cHelperRings);
for (int atom=0; atom<mol.getAtoms(); atom++) {
try {
long type = AtomTypeCalculator.getAtomType(mol, atom, ATOM_TYPE_MODE);
int index = sSortedTypeList.getIndex(type);
if (index != -1)
cLogP += INCREMENT[index];
// else
// System.out.println("type not found for atom "+atom+":"+Long.toHexString(type)+" "+AtomTypeCalculator.getTypeString(type, ATOM_TYPE_MODE));
}
catch (Exception e) {} // unsupported atom type exceptions are tolerable
}
return cLogP;
}
/**
* Normalizes ambiguous bonds and assigns cLogP increments to every atom
* based on its enhanced atom type.
* @param mol
* @param increment not smaller than non-H atom count of mol
* @return
*/
public void getCLogPIncrements(StereoMolecule mol, float[] increment) {
mol.normalizeAmbiguousBonds();
mol.ensureHelperArrays(Molecule.cHelperRings);
for (int atom=0; atom<mol.getAtoms(); atom++) {
try {
int index = sSortedTypeList.getIndex(AtomTypeCalculator.getAtomType(mol, atom, ATOM_TYPE_MODE));
if (index != -1)
increment[atom] = INCREMENT[index];
}
catch (Exception e) {} // unsupported atom type exceptions are tolerable
}
}
public ParameterizedStringList getDetail(StereoMolecule mol) {
ParameterizedStringList detail = new ParameterizedStringList();
detail.add("cLogP Values are estimated applying an atom-type based increment system.",
ParameterizedStringList.cStringTypeText);
detail.add("Atom-types are 64-bit numbers describing atoms and their near surrounding.",
ParameterizedStringList.cStringTypeText);
detail.add("Recognized atom types and their contributions are:",ParameterizedStringList.cStringTypeText);
mol.normalizeAmbiguousBonds();
mol.ensureHelperArrays(Molecule.cHelperRings);
if (mol != null) {
int errorCount = 0;
TreeMap<Long,Integer> countMap = new TreeMap<Long,Integer>();
NumberFormat formatter = new DecimalFormat("#0.000");
for (int atom=0; atom<mol.getAtoms(); atom++) {
try {
long atomType = AtomTypeCalculator.getAtomType(mol, atom, ATOM_TYPE_MODE);
Integer typeCount = countMap.get(new Long(atomType));
if (typeCount == null)
countMap.put(new Long(atomType), new Integer(1));
else
countMap.put(new Long(atomType), new Integer(typeCount.intValue()+1));
}
catch (Exception e) {
errorCount++;
}
}
if (errorCount != 0)
detail.add("Warning: "+errorCount + " atom type(s) could not be determined.", ParameterizedStringList.cStringTypeText);
for (Long type:countMap.keySet()) {
if (sSortedTypeList.contains(type))
detail.add(countMap.get(type) + " * "+
formatter.format(INCREMENT[sSortedTypeList.getIndex(type)]) + " AtomType: 0x" + Long.toHexString(type),ParameterizedStringList.cStringTypeText);
else
detail.add("Warning: For atom type 0x"+Long.toHexString(type)+" ("+countMap.get(type)+" times found) is no increment available.", ParameterizedStringList.cStringTypeText);
}
}
return detail;
}
}
