Cyndi: a multi-objective evolution algorithm based method for bioactive molecular conformational generation

Background Conformation generation is a ubiquitous problem in molecule modelling. Many applications require sampling the broad molecular conformational space or perceiving the bioactive conformers to ensure success. Numerous in silico methods have been proposed in an attempt to resolve the problem,...

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Vydané v:BMC bioinformatics Ročník 10; číslo 1; s. 101
Hlavní autori: Liu, Xiaofeng, Bai, Fang, Ouyang, Sisheng, Wang, Xicheng, Li, Honglin, Jiang, Hualiang
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London BioMed Central 31.03.2009
BioMed Central Ltd
BMC
Predmet:
Algorithms
Applications software
Bioinformatics
Biomedical and Life Sciences
Computational biology
Computational Biology/Bioinformatics
Computer Appl. in Life Sciences
Computer Simulation
Conformation
Databases, Factual
Drug Design
Life Sciences
Methodology
Methodology Article
Microarrays
Models, Molecular
Molecular Conformation
Proteins
Software
China
Root Mean Square Deviation
Pareto Frontier
Conformational Space
Pareto Front
Pareto Optimal Solution
ISSN:1471-2105, 1471-2105
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Shrnutí:Background Conformation generation is a ubiquitous problem in molecule modelling. Many applications require sampling the broad molecular conformational space or perceiving the bioactive conformers to ensure success. Numerous in silico methods have been proposed in an attempt to resolve the problem, ranging from deterministic to non-deterministic and systemic to stochastic ones. In this work, we described an efficient conformation sampling method named Cyndi, which is based on multi-objective evolution algorithm. Results The conformational perturbation is subjected to evolutionary operation on the genome encoded with dihedral torsions. Various objectives are designated to render the generated Pareto optimal conformers to be energy-favoured as well as evenly scattered across the conformational space. An optional objective concerning the degree of molecular extension is added to achieve geometrically extended or compact conformations which have been observed to impact the molecular bioactivity ( J Comput -Aided Mol Des 2002, 16: 105–112). Testing the performance of Cyndi against a test set consisting of 329 small molecules reveals an average minimum RMSD of 0.864 Å to corresponding bioactive conformations, indicating Cyndi is highly competitive against other conformation generation methods. Meanwhile, the high-speed performance (0.49 ± 0.18 seconds per molecule) renders Cyndi to be a practical toolkit for conformational database preparation and facilitates subsequent pharmacophore mapping or rigid docking. The copy of precompiled executable of Cyndi and the test set molecules in mol2 format are accessible in Additional file 1. Conclusion On the basis of MOEA algorithm, we present a new, highly efficient conformation generation method, Cyndi, and report the results of validation and performance studies comparing with other four methods. The results reveal that Cyndi is capable of generating geometrically diverse conformers and outperforms other four multiple conformer generators in the case of reproducing the bioactive conformations against 329 structures. The speed advantage indicates Cyndi is a powerful alternative method for extensive conformational sampling and large-scale conformer database preparation.
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ISSN:1471-2105
1471-2105
DOI:10.1186/1471-2105-10-101