Comparing performance of computational tools for combinatorial library design

被引:14
作者
Evensen, E [1 ]
Eksterowicz, JE [1 ]
Stanton, RV [1 ]
Oshiro, C [1 ]
Grootenhuis, PDJ [1 ]
Bradley, EK [1 ]
机构
[1] Deltagen Res Labs, Redwood City, CA 94063 USA
关键词
D O I
10.1021/jm025618t
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In using computational tools for library design it is necessary to understand the performance and limitations of available methods. This letter reports systematic comparisons of applying ligand-based and structure-based tools across therapeutic project-derived data sets. Included are assessments of performance in real-world iterative design applications and the utility of target structural information. The results suggest that combining screening and target structure information is robust; further, a well-designed screening library can compensate for lacking structural information.
引用
收藏
页码:5125 / 5128
页数:4
相关论文
共 26 条
[1]   The design of combinatorial libraries using properties and 3D pharmacophore fingerprints [J].
Beno, BR ;
Mason, JS .
DRUG DISCOVERY TODAY, 2001, 6 (05) :251-258
[2]   Protein-based virtual screening of chemical databases. 1. Evaluation of different docking/scoring combinations [J].
Bissantz, C ;
Folkers, G ;
Rognan, D .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (25) :4759-4767
[3]   A rapid computational method for lead evolution:: Description and application to α1-adrenergic antagonists [J].
Bradley, EK ;
Beroza, P ;
Penzotti, JE ;
Grootenhuis, PDJ ;
Spellmeyer, DC ;
Miller, JL .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (14) :2770-2774
[4]   Informative library design as an efficient strategy to identify and optimize leads: Application to cyclin-dependent kinase 2 antagonists [J].
Bradley, EK ;
Miller, JL ;
Saiah, E ;
Grootenhuis, PDJ .
JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (20) :4360-4364
[5]   Consensus scoring: A method for obtaining improved hit rates from docking databases of three-dimensional structures into proteins [J].
Charifson, PS ;
Corkery, JJ ;
Murcko, MA ;
Walters, WP .
JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (25) :5100-5109
[6]   Consensus scoring for ligand/protein interactions [J].
Clark, RD ;
Strizhev, A ;
Leonard, JM ;
Blake, JF ;
Matthew, JB .
JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2002, 20 (04) :281-295
[7]   Coupling structure-based design with combinatorial chemistry: application of active site derived pharmacophores with informative library design [J].
Eksterowicz, JE ;
Evensen, E ;
Lemmen, C ;
Brady, GP ;
Lanctot, JK ;
Bradley, EK ;
Saiah, E ;
Robinson, LA ;
Grootenhuis, PDJ ;
Blaney, JM .
JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2002, 20 (06) :469-477
[8]   DOCK 4.0: Search strategies for automated molecular docking of flexible molecule databases [J].
Ewing, TJA ;
Makino, S ;
Skillman, AG ;
Kuntz, ID .
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2001, 15 (05) :411-428
[9]   High throughput screening for drug discovery: Continually transitioning into new technology [J].
Fox, S ;
Farr-Jones, S ;
Yund, MA .
JOURNAL OF BIOMOLECULAR SCREENING, 1999, 4 (04) :183-186
[10]   ITERATIVE PARTIAL EQUALIZATION OF ORBITAL ELECTRONEGATIVITY - A RAPID ACCESS TO ATOMIC CHARGES [J].
GASTEIGER, J ;
MARSILI, M .
TETRAHEDRON, 1980, 36 (22) :3219-3228