A computational ONIOM model for the description of the H-bond interactions between NU2058 analogues and CDK2 active site

被引：18

作者：

Alzate-Morales, Jans H. ^{[1
]}

Caballero, Julio ^{[1
]}

Gonzalez-Nilo, Fernando D. ^{[1
]}

Contreras, Renato ^{[2
]}

机构：

[1] Univ Talca, Ctr Bioinformat & Simulac Mol, Casilla 721, Chile

[2] Univ Chile, Fac Sci, Dept Chem, Theoret Chem Grp, Santiago, Chile

来源：

CHEMICAL PHYSICS LETTERS | 2009年 / 479卷 / 1-3期

关键词：

DEPENDENT KINASE INHIBITORS; STRUCTURE-BASED DESIGN; SEMIEMPIRICAL METHODS; 2D AUTOCORRELATION; CELL-CYCLE; N-BUTANE; OPTIMIZATION; DERIVATIVES; ENERGY; PREDICTION;

D O I：

10.1016/j.cplett.2009.08.020

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070305 [高分子化学与物理];

摘要：

The ONIOM method was applied to study the hydrogen bond interactions between some CDK2 inhibitors and various models of the active site in CDK2/CyclinA system. It was found that according with the model's size, a good description of the molecular interactions inside the active site can be obtained. From best model, it was possible to obtain a reliable correlation between the total ONIOM energy and the biological activity reported for compounds studied. The results show that H-bond interaction energy is the principal component in this protein-ligand interaction and residues Lys89 and Asp86 are essential for great potency of compound NU6102. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：149 / 155

页数：7

共 31 条

[1]

A computational study of the protein-ligand interactions in CDK2 inhibitors:: Using quantum mechanics/molecular mechanics interaction energy as a predictor of the biological activity [J].

Alzate-Morales, Jans H. ;

Contreras, Renato ;

Soriano, Alejandro ;

Tunon, Inaki ;

Silla, Estanislao .

BIOPHYSICAL JOURNAL, 2007, 92 (02) :430-439

[2]

Insights into the Structural Basis of N2 and O6 Substituted Guanine Derivatives as Cyclin-Dependent Kinase 2 (CDK2) Inhibitors: Prediction of the Binding Modes and Potency of the inhibitors by Docking and ONIOM Calculations [J].

Alzate-Morales, Jans H. ;

Caballero, Julio ;

Vergara Jague, Ariela ;

Gonzalez Nilo, Fernando D. .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2009, 49 (04) :886-899

[3]

Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles [J].

Arris, CE ;

Boyle, FT ;

Calvert, AH ;

Curtin, NJ ;

Endicott, JA ;

Garman, EF ;

Gibson, AE ;

Golding, BT ;

Grant, S ;

Griffin, RJ ;

Jewsbury, P ;

Johnson, LN ;

Lawrie, AM ;

Newell, DR ;

Noble, MEM ;

Sausville, EA ;

Schultz, R ;

Yu, W .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (15) :2797-2804

[4]

Structural requirements of pyrido[2,3-d]pyrimidin-7-one as CDK4/D inhibitors:: 2D autocorrelation, CoMFA and CoMSIA analyses [J].

Caballero, Julio ;

Fernandez, Michael ;

Gonzalez-Nilo, Fernando D. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (11) :6103-6115

[5]

Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor [J].

Davies, TG ;

Bentley, J ;

Arris, CE ;

Boyle, FT ;

Curtin, NJ ;

Endicott, JA ;

Gibson, AE ;

Golding, BT ;

Griffin, RJ ;

Hardcastle, IR ;

Jewsbury, P ;

Johnson, LN ;

Mesguiche, V ;

Newell, DR ;

Noble, MEM ;

Tucker, JA ;

Wang, L ;

Whitfield, HJ .

NATURE STRUCTURAL BIOLOGY, 2002, 9 (10) :745-749

[6]

Structure-based design of cyclin-dependent kinase inhibitors [J].

Davies, TG ;

Pratt, DJ ;

Endicott, JA ;

Johnson, LN ;

Noble, MEM .

PHARMACOLOGY & THERAPEUTICS, 2002, 93 (2-3) :125-133

[7]

Topochemical models for prediction of cyclin-dependent kinase 2 inhibitory activity of indole-2-ones [J].

Dureja, H ;

Madan, AK .

JOURNAL OF MOLECULAR MODELING, 2005, 11 (06) :525-531

[8]

Modeling of cyclin-dependent kinase inhibition by 1H-pyrazolo[3,4-d]pyrimidine derivatives using artificial neural network ensembles [J].

Fernández, M ;

Tudidor-Camba, A ;

Caballero, J .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2005, 45 (06) :1884-1895

[9]

Frisch M.J., 2001, GAUSSIAN 98 REVISION

[10]

2D autocorrelation modelling of the inhibitory activity of cytokinin-derived cyclin-dependent kinase inhibitors [J].

Gonzalez, Maykel Perez ;

Caballero, Julio ;

Morales Helguera, Aliuska ;

Garriga, Miguel ;

Gonzalez, Gerardo ;

Fernandez, Michael .

BULLETIN OF MATHEMATICAL BIOLOGY, 2006, 68 (04) :735-751

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