Acta Chimica Sinica ›› 2013, Vol. 71 ›› Issue (04): 593-601.DOI: 10.6023/A13010015 Previous Articles     Next Articles



廖晨伊, 周健   

  1. 华南理工大学化学与化工学院 广东省绿色化学产品技术重点实验室 广州 510640
  • 投稿日期:2013-01-04 发布日期:2013-03-01
  • 通讯作者: 周健
  • 基金资助:

    项目受教育部新世纪优秀人才支持计划(No. NCET-07-0313)、国家自然科学基金(No. 20876052)及广东省自然科学基金(No. S2011010002078)资助.

Replica Exchange Molecular Dynamics Simulations on the Folding of Trpzip4 β-Hairpin

Liao Chenyi, Zhou Jian   

  1. School of Chemistry and Chemical Engineering, Guangdong Provincial Key Lab for Green Chemical Product Technology, South China University of Technology, Guangzhou 510640
  • Received:2013-01-04 Published:2013-03-01
  • Supported by:

    Project supported by the Program for New Century Excellent Talents in Universities, Ministry of Education, China (No. NCET-07-0313), the National Natural Science Foundation of China (No. 20876052) and the Natural Science Foundation of Guangdong Province(No. S2011010002078).

β-Hairpin is an essential secondary structure unit of protein. Understanding the formation mechanism of the β hairpin and kinetic stability helps to gain insight into the formation of protein secondary structure as well as the mechanism of protein folding. Replica exchange molecular dynamics (REMD) approach is applied to investigate the folding mechanism of Trpzip4 β-hairpin. The REMD method is more efficient than conventional MD in searching for a representative set of the low energy minima in the existence of a large energy gap between the native state and any of the other possible state. The potential energy, backbone RMSD and solvent-accessible surface area (SASA) present descending trends in the process of REMD at 288 K. Methyl groups (most in threonines) show hydrophobic interactions with SASA decrements. The hydrophobic interactions and intra hydrogen bond forming drive the folding and maintain the low energy structure. Two low energy structures, β-hairpin and helix-coil conformation, are sampled by REMD. In β-hairpin structure, the hydroxyl group (OH) of Thr49 at β turn is accessible to form hydrogen bonds with carboxyl group (COO-) or C=O group of Asp46; while the hydroxyl group (OH) of Thr51 is inclined to interact with water molecule with methyl orienting inwards. As a result, the strong interactions between Asp46 and Thr49 cause a bend at β turn. In helix-coil conformation, hydrophobic interactions play between indole ring and methyl group. One of the zip-in paths of Trpzip4 indicates that, the forming of hydrogen bonds at β turn affects the whole folding process of β hairpin. The forming of hydrogen bonds at β turn takes place first, since it has advantages of distance and strong interactions in both side chains and backbone. Total solvent-accessible surface area decreases significantly as it folds to the β hairpin structure. REMD method could sample large phase space for the low energy minima, and present scenarios of potential energy distribution on phase space with related variables as hydrophobic SASA, backbone RMSD, and hydrogen bonds for specific conformation. This work sheds some lights on the understanding of β hairpin folding.

Key words: β-hairpin, folding, replica exchange molecular dynamics, hydrogen bond, hydrophobic interaction