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

doi:10.1186/1471-2105-10-101

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Cyndi: a multi-objective evolution algorithm based method for bioactive molecular conformational generation
	Liu, Xiaofeng 1; Bai, Fang 2,4; Ouyang, Sisheng 1; Wang, Xicheng 2; Li, Honglin 1,2,3; Jiang, Hualiang1,3
刊名	BMC BIOINFORMATICS
	2009-03-31
卷号	10
ISSN号	1471-2105
DOI	10.1186/1471-2105-10-101
文献子类	Article
英文摘要	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 angstrom 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.
资助项目	National Natural Science Foundation of China[20803022] ; National Natural Science Foundation of China[30672539] ; National Natural Science Foundation of China[20721003] ; Shanghai Committee of Science and Technology[07dz22004] ; 863 Hi-Tech Program of China[2007AA02Z304] ; International Collaboration Project of China[2007DFB30370] ; National Basic Research Program of China[2009CB918501] ; National Basic Research Program of China[2009CB918502] ; Chinese Academy of Sciences[SIMM0709QN-09]
WOS关键词	PROTEIN-BOUND LIGANDS ; DRUG-LIKE MOLECULES ; GENETIC ALGORITHM ; OPTIMIZATION TECHNIQUES ; TEST SET ; DOCKING ; COVERAGE ; SPACE ; FLEXIBILITY ; DATABASE
WOS研究方向	Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Mathematical & Computational Biology
语种	英语
出版者	BMC
WOS记录号	WOS:000266604200002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279286]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Li, Honglin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 2.Dalian Univ Technol, State Key Lab Struct Anal Ind Equipment, Dept Engn Mech, Dalian 116023, Peoples R China; 3.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 4.Dalian Univ Technol, Dept Chem Engn, Dalian 116012, Peoples R China
推荐引用方式 GB/T 7714	Liu, Xiaofeng,Bai, Fang,Ouyang, Sisheng,et al. Cyndi: a multi-objective evolution algorithm based method for bioactive molecular conformational generation[J]. BMC BIOINFORMATICS,2009,10.
APA	Liu, Xiaofeng,Bai, Fang,Ouyang, Sisheng,Wang, Xicheng,Li, Honglin,&Jiang, Hualiang.(2009).Cyndi: a multi-objective evolution algorithm based method for bioactive molecular conformational generation.BMC BIOINFORMATICS,10.
MLA	Liu, Xiaofeng,et al."Cyndi: a multi-objective evolution algorithm based method for bioactive molecular conformational generation".BMC BIOINFORMATICS 10(2009).