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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 24期

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