Conformational Sampling of Flexible Ligand-binding Protein Loops

Bulletin of the Korean chemical society

Woong-Hee Shin¹  Seokmin Shin¹  Gyu Rie Lee¹  Chaok Seok¹  Hahnbeom Park¹ 

关键词: Loop modeling;    Ligand binding;    Conformational change;    Conformational sampling;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Protein loops are often involved in diverse biological functions, and some functional loops show conformational changes upon ligand binding. Since this conformational change is directly related to ligand binding pose and protein function, there have been numerous attempts to predict this change accurately. In this study, we show that it is plausible to obtain meaningful ensembles of loop conformations for flexible, ligand-binding protein loops efficiently by applying a loop modeling method. The loop modeling method employs triaxial loop closure algorithm for trial conformation generation and conformational space annealing for global energy optimization. When loop modeling was performed on the framework of ligand-free structure, loop structures within 3 Å RMSD from the crystal loop structure for the ligand-bound state were sampled in 4 out of 6 cases. This result is encouraging considering that no information on the ligand-bound state was used during the loop modeling process. We therefore expect that the present loop modeling method will be useful for future developments of flexible protein-ligand docking methods.

【 授权许可】

Unknown