Conformational Selection versus Induced Fit in Kinases: The Case of PI3K-γ

被引：13

作者：

D'Abramo, Marco ^{[1
]}

Rabal, Obdulia ^{[2
]}

Oyarzabal, Julen ^{[2
]}

Gervasio, Francesco Luigi ^{[1
]}

机构：

[1] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Programme, Madrid 28029, Spain

[2] Spanish Natl Canc Res Ctr CNIO, Expt Therapeut Programme, Madrid 28029, Spain

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2012年 / 51卷 / 03期

关键词：

conformational selection; induced fit; kinases; molecular dynamics; molecular recognition; FORCE-FIELDS; BINDING; DYNAMICS; TRANSITIONS; RECOGNITION; INHIBITOR; MECHANISM;

D O I：

10.1002/anie.201103264

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Kinase binding: The mechanism of molecular recognition in the pharmacologically relevant phosphoinositide 3-kinase PI3K-γ has been investigated. The analysis of molecular dynamics simulations, free energy calculations, and docking interactions suggests that a combination of two proposed limiting mechanisms, conformational selection and induced fit, may best explain binding events between the ligand and its target. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：642 / 646

页数：5

共 35 条

[1] ESSENTIAL DYNAMICS OF PROTEINS [J].

AMADEI, A ;

LINSSEN, ABM ;

BERENDSEN, HJC .

PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1993, 17 (04) :412-425

[2]

Berndt A, 2010, NAT CHEM BIOL, V6, P117, DOI [10.1038/nchembio.293, 10.1038/NCHEMBIO.293]

[3] Protein Conformational Transitions: The Closure Mechanism of a Kinase Explored by Atomistic Simulations [J].

Berteotti, Anna ;

Cavalli, Andrea ;

Branduardi, Davide ;

Gervasio, Francesco Luigi ;

Recanatini, Maurizio ;

Parrinello, Michele .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (01) :244-250

[4] Are current molecular dynamics force fields too helical? [J].

Best, Robert B. ;

Buchete, Nicolae-Viorel ;

Hummer, Gerhard .

BIOPHYSICAL JOURNAL, 2008, 95 (01) :L7-L9

[5] The role of dynamic conformational ensembles in biomolecular recognition [J].

Boehr, David D. ;

Nussinov, Ruth ;

Wright, Peter E. .

NATURE CHEMICAL BIOLOGY, 2009, 5 (11) :789-796

[6] Canonical sampling through velocity rescaling [J].

Bussi, Giovanni ;

Donadio, Davide ;

Parrinello, Michele .

JOURNAL OF CHEMICAL PHYSICS, 2007, 126 (01)

[7] Folding for binding or binding for folding? [J].

Caflisch, A .

TRENDS IN BIOTECHNOLOGY, 2003, 21 (10) :423-425

[8] The PI3K inhibitor arsenal: choose your weapon! [J].

Crabbe, Tom ;

Welham, Melanie J. ;

Ward, Stephen G. .

TRENDS IN BIOCHEMICAL SCIENCES, 2007, 32 (10) :450-456

[9] Coupling of folding and binding for unstructured proteins [J].

Dyson, HJ ;

Wright, PE .

CURRENT OPINION IN STRUCTURAL BIOLOGY, 2002, 12 (01) :54-60

[10]

Fersht A., 1999, Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding

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