Document Detail

A new method for the gradient-based optimization of molecular complexes.
MedLine Citation:
PMID:  19031415     Owner:  NLM     Status:  MEDLINE    
We present a novel method for the local optimization of molecular complexes. This new approach is especially suited for usage in molecular docking. In molecular modeling, molecules are often described employing a compact representation to reduce the number of degrees of freedom. This compact representation is realized by fixing bond lengths and angles while permitting changes in translation, orientation, and selected dihedral angles. Gradient-based energy minimization of molecular complexes using this representation suffers from well-known singularities arising during the optimization process. We suggest an approach new in the field of structure optimization that allows to employ gradient-based optimization algorithms for such a compact representation. We propose to use exponential mapping to define the molecular orientation which facilitates calculating the orientational gradient. To avoid singularities of this parametrization, the local minimization algorithm is modified to change efficiently the orientational parameters while preserving the molecular orientation, i.e. we perform well-defined jumps on the objective function. Our approach is applicable to continuous, but not necessarily differentiable objective functions. We evaluated our new method by optimizing several ligands with an increasing number of internal degrees of freedom in the presence of large receptors. In comparison to the method of Solis and Wets in the challenging case of a non-differentiable scoring function, our proposed method leads to substantially improved results in all test cases, i.e. we obtain better scores in fewer steps for all complexes.
Jan Fuhrmann; Alexander Rurainski; Hans-Peter Lenhof; Dirk Neumann
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of computational chemistry     Volume:  30     ISSN:  1096-987X     ISO Abbreviation:  J Comput Chem     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-04-30     Completed Date:  2009-07-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9878362     Medline TA:  J Comput Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1371-8     Citation Subset:  IM    
Copyright Information:
(c) 2008 Wiley Periodicals, Inc.
Center for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
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MeSH Terms
Computer Simulation*
Models, Chemical*
Quantum Theory
Reg. No./Substance:

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