Applying flexible molecular docking to simulate protein retention behavior in hydrophobic interaction chromatography

作     者：ZHOU Peng1, TIAN FeiFei1 & LI ZhiLiang1,2 1 College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, China 2 State Key Laboratory of Chemo/Biosensing and Chemometrics, Changsha 410082, China 

作者机构：College of Chemistry and Chemical Engineering Chongqing University Chongqing China State Key Laboratory of Chemo/Biosensing and Chemometrics Changsha China 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2007年第50卷第5期

页      面：675-682页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：Supported by National Project 863 Fund (Grant No. 2006AA02Z312) State Key Laboratory of Chemo Biosensing and Chemometrics Foundation (Grant No. 0501201) 

主　　题：hydrophobic interaction chromatography, flexible molecular docking, genetic algorithm, protein, salting-in factor 

摘      要：Interaction between proteins and stationary phase in hydrophobic interaction chromatography (HIC) is differentiated into two thermodynamic processes involving direct nonbonding/conformation interac- tion and surface hydrophobic effect of proteins, hence quantitatively giving rise to a binary linear rela- tion between HIC retention time (RT) at concentrated salting liquid and ligand-protein binding free en- ergy. Then, possible binding manners for 27 proteins of known crystal structures with hydrophobic ligands are simulated and analyzed via ICM flexible molecular docking and genetic algorithm, with re- sults greatly consistent with experimental values. By investigation, it is confirmed local hydrophobic effects of proteins and nonbinding/conformation interaction between ligand and protein both notably influence HIC chromatogram retention behaviors, mainly focusing on exposed portions on the protein surface.