Simple Size-Independent Measure of Ligand Efficiency

被引：82

作者：

Nissink, J. Willem M. ^{[1
]}

机构：

[1] Astrazeneca, Computat Chem, Macclesfield SK10 4TG, Cheshire, England

来源：

JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2009年 / 49卷 / 06期

关键词：

DRUG DESIGN; INHIBITORS; DATABASE;

D O I：

10.1021/ci900094m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This paper suggests a functional form for a size-independent ligand efficiency (LE) measure of the form SILE = affinity/N(0.3), where N is the number of heavy atoms. The size-dependency effect of the commonly used LE measure (LE = affinity/N) is apparent in experimental settings like hit-to-lead optimization, but equally well applies to in-silico binding-energy-based estimates. It is therefore expected that the correction is useful in experimental drug optimization, as well as in in-silico applications like protein-ligand docking.

引用

页码：1617 / 1622

页数：6

共 14 条

[1] Structure-based thermodynamic analysis of HIV-1 protease inhibitors [J].

Bardi, JS ;

Luque, I ;

Freire, E .

BIOCHEMISTRY, 1997, 36 (22) :6588-6596

[2] The Binding Database: data management and interface design [J].

Chen, X ;

Lin, YM ;

Liu, M ;

Gilson, MK .

BIOINFORMATICS, 2002, 18 (01) :130-139

[3] Fragment-based drug design: How big is too big? [J].

Hajduk, Philip J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (24) :6972-6976

[4] Fragment-Based Design of Small Molecule X-Linked Inhibitor of Apoptosis Protein Inhibitors [J].

Huang, Jui-Wen ;

Zhang, Ziming ;

Wu, Bainan ;

Cellitti, Jason F. ;

Zhang, Xiyun ;

Dahl, Russell ;

Shiau, Chung-Wai ;

Welsh, Kate ;

Emdadi, Aras ;

Stebbins, John L. ;

Reed, John C. ;

Pellecchia, Maurizio .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (22) :7111-7118

[5] The maximal affinity of ligands [J].

Kuntz, ID ;

Chen, K ;

Sharp, KA ;

Kollman, PA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (18) :9997-10002

[6] A widely applicable set of descriptors [J].

Labute, P .

JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2000, 18 (4-5) :464-477

[7] BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities [J].

Liu, Tiqing ;

Lin, Yuhmei ;

Wen, Xin ;

Jorissen, Robert N. ;

Gilson, Michael K. .

NUCLEIC ACIDS RESEARCH, 2007, 35 :D198-D201

[8] Novel arylsulfonamides possessing sub-picomolar HIV protease activities and potent anti-HIV activity against wild-type and drug-resistant viral strains [J].

Miller, JF ;

Furfine, ES ;

Hanlon, MH ;

Hazen, RJ ;

Ray, JA ;

Robinson, L ;

Samano, V ;

Spaltenstein, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (04) :959-963

[9] THERMODYNAMICS OF STRUCTURAL STABILITY AND COOPERATIVE FOLDING BEHAVIOR IN PROTEINS [J].

MURPHY, KP ;

FREIRE, E .

ADVANCES IN PROTEIN CHEMISTRY, 1992, 43 :313-361

[10] Thermodynamics of protein-ligand interactions: History, presence, and future aspects [J].

Perozzo, R ;

Folkers, G ;

Scapozza, L .

JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION, 2004, 24 (1-2) :1-52

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