SLATE: A method for the superposition of flexible ligands

被引:30
作者
Mills, JEJ [1 ]
de Esch, IJP [1 ]
Perkins, TDJ [1 ]
Dean, PM [1 ]
机构
[1] Univ Cambridge, Dept Pharmacol, Drug Design Grp, Cambridge CB2 1QJ, England
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
drug design; flexible ligands; ligand-receptor interaction; receptor model; superposition;
D O I
10.1023/A:1011102129244
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A novel program for the superposition of flexible molecules, slate, is presented. It uses simulated annealing to minimise the difference between the distance matrices calculated from the hydrogen-bonding and aromatic-ring properties of two ligands. A method for generating a molecular stack using multiple pairwise matches is illustrated. These stacks are used by the program doh to predict the relative positions of receptor atoms that could form hydrogen bonds to two or more ligands in the dataset. The methodology has been applied to ligands binding to dihydrofolate reductase, thermolysin, H-3 histamine receptors, alpha (2) adrenoceptors and 5-HT1D receptors. When there are sufficient numbers and diversity of molecules in the dataset, the prediction of receptor-atom positions is applicable to compound design.
引用
收藏
页码:81 / 96
页数:16
相关论文
共 43 条
  • [1] THE DEVELOPMENT OF VERSION-3 AND VERSION-4 OF THE CAMBRIDGE STRUCTURAL DATABASE SYSTEM
    ALLEN, FH
    DAVIES, JE
    GALLOY, JJ
    JOHNSON, O
    KENNARD, O
    MACRAE, CF
    MITCHELL, EM
    MITCHELL, GF
    SMITH, JM
    WATSON, DG
    [J]. JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1991, 31 (02): : 187 - 204
  • [2] [Anonymous], P INT C COMP AID DES
  • [3] THE MATCHING OF ELECTROSTATIC EXTREMA - A USEFUL METHOD IN DRUG DESIGN - A STUDY OF PHOSPHODIESTERASE-III INHIBITORS
    APAYA, RP
    LUCCHESE, B
    PRICE, SL
    VINTER, JG
    [J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1995, 9 (01) : 33 - 43
  • [4] AUTO-INHIBITION OF BRAIN HISTAMINE-RELEASE MEDIATED BY A NOVEL CLASS (H-3) OF HISTAMINE-RECEPTOR
    ARRANG, JM
    GARBARG, M
    SCHWARTZ, JC
    [J]. NATURE, 1983, 302 (5911) : 832 - 837
  • [5] MOLECULAR-STRUCTURE MATCHING BY SIMULATED ANNEALING .1. A COMPARISON BETWEEN DIFFERENT COOLING SCHEDULES
    BARAKAT, MT
    DEAN, PM
    [J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1990, 4 (03) : 295 - 316
  • [6] PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES
    BERNSTEIN, FC
    KOETZLE, TF
    WILLIAMS, GJB
    MEYER, EF
    BRICE, MD
    RODGERS, JR
    KENNARD, O
    SHIMANOUCHI, T
    TASUMI, M
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1977, 112 (03) : 535 - 542
  • [7] Conformational energy penalties of protein-bound ligands
    Bostrom, J
    Norrby, PO
    Liljefors, T
    [J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1998, 12 (04) : 383 - 396
  • [8] Evolutionary algorithms in computer-aided molecular design
    Clark, DE
    Westhead, DR
    [J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1996, 10 (04) : 337 - 358
  • [9] THE SEARCH FOR FUNCTIONAL CORRESPONDENCES IN MOLECULAR-STRUCTURE BETWEEN 2 DISSIMILAR MOLECULES
    DANZIGER, DJ
    DEAN, PM
    [J]. JOURNAL OF THEORETICAL BIOLOGY, 1985, 116 (02) : 215 - 224
  • [10] De Esch IJP, 1998, PHARM LIBR, V30, P223