Generative Models for Chemical Structures

被引:18
作者
White, David [2 ]
Wilson, Richard C. [1 ]
机构
[1] Univ York, Dept Comp Sci, York Y010 5DD, N Yorkshire, England
[2] Otto Friedrich Univ Bamberg, Software Technol Res Grp, D-96047 Bamberg, Germany
关键词
DE-NOVO DESIGN; MEDIAN GRAPHS; PROGRAM; DOCKING; VALIDATION; ALGORITHM; DATABASES; SPACE;
D O I
10.1021/ci9004089
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
We apply recently developed techniques for pattern recognition to construct a generative model for chemical structure. This approach can be viewed as ligand-based de novo design. We construct a statistical model describing the structural variations present in a set of molecules which may be sampled to generate new structurally similar examples. We prevent the possibility of generating chemically invalid molecules, according to our implicit hydrogen model, by projecting samples onto the nearest chemically valid molecule. By populating the input set with molecules that are active against a target, we show how new molecules may be generated that will likely also be active against the target.
引用
收藏
页码:1257 / 1274
页数:18
相关论文
共 54 条
[1]   Can we learn to distinguish between "drug-like" and "nondrug-like" molecules? [J].
Ajay ;
Walters, WP ;
Murcko, MA .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (18) :3314-3324
[2]  
[Anonymous], 1990, M 196 1988 LOS ANG C
[3]  
[Anonymous], 2009, FRED FAST RIG EXH DO
[4]   APPLICATIONS OF GRAPH-THEORY IN CHEMISTRY [J].
BALABAN, AT .
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1985, 25 (03) :334-343
[5]   Molecular complexity analysis of de novo designed ligands [J].
Boda, Krisztina ;
Johnson, A. Peter .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (20) :5869-5879
[6]   An eigenspace projection clustering method for inexact graph matching [J].
Caelli, T ;
Kosinov, S .
IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE, 2004, 26 (04) :515-519
[7]   STRUCTURE GENERATION BY REDUCTION - A NEW STRATEGY FOR COMPUTER-ASSISTED STRUCTURE ELUCIDATION [J].
CHRISTIE, BD ;
MUNK, ME .
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1988, 28 (02) :87-93
[8]   MOLMAKER: De novo generation of 3D databases for use in drug design [J].
Clark, DE ;
Firth, MA ;
Murray, CW .
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1996, 36 (01) :137-145
[9]   BOOMSLANG: A program for combinatorial structure generation [J].
Cosgrove, DA ;
Kenny, PW .
JOURNAL OF MOLECULAR GRAPHICS, 1996, 14 (01) :1-&
[10]   Median graphs: A genetic approach based on new theoretical properties [J].
Ferrer, M. ;
Valveny, E. ;
Serratosa, F. .
PATTERN RECOGNITION, 2009, 42 (09) :2003-2012