Folding of EK peptide and its dependence on salt concentration and pH: A computational study  

作　　者：MEI Ye ZHANG DaWei DUAN Li ZHANG QingGang ZHANG John ZengHui 

机构地区：[1]State Key Laboratory of Precision Spectroscopy, East China Normal University, Shanghai 200062, China [2]Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China [3]Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore [4]College of Physics and Electronics, Shandong Normal University, Jinan 250014, China [5]Department of Chemistry, New York University, New York 10003, USA

出　　处：《Science China Chemistry》2011年第12期1974-1981,共8页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China (20803034);the Shanghai Rising-Star Program;supported by the Nanyang Technological University Start-up (M58110043);support from the National Natural Science Foundation of China (20933002);Shanghai Pujiang Program (09PJ1404000)

摘　　要：In this study, we apply both palrwise AMBER03 force field and the recently developed polarized force field to study the folding process of EK peptide under various ion strength and pH conditions. The polarized force field is based on our newly proposed adaptive hydrogen bond-specific charge （AHBC） scheme. These two force fields differ only by the atomic charges. Solvent effect is described with generalized Born models （IGB5 in AMBER 10 package）. The result shows that although when applying AMBER03 charge, the helical structure is preferred, its dependence on salt concentration and pH is qualitatively wrong. While using AHBC the peptide finds its native structure within 10 ns, and then fluctuates around this folded state. Under high salt concentration or extreme pH conditions the calculated helical structure probability drops, which is in qualitative agreement with the experiment. Analysis of the atomic charges and the interaction between the donor-acceptor pair in main hydrogen bonds shows that the helical structure is stabilized when polarization effect is counted. It again shows that polarization effect is a very important improvement over traditional force field and is essential for protein folding. We also prove that the salt bridge interaction between 4-residue apart GLU and LYS residues is not critical to the stability of helical structure of EK peptide, but is merely an auxiliary factor, also in agreement with the experiment.In this study,we apply both pairwise AMBER03 force field and the recently developed polarized force field to study the folding process of EK peptide under various ion strength and pH conditions.The polarized force field is based on our newly proposed adaptive hydrogen bond-specific charge(AHBC) scheme.These two force fields differ only by the atomic charges.Solvent effect is described with generalized Born models(IGB5 in AMBER 10 package).The result shows that although when applying AMBER03 charge,the helical structure is preferred,its dependence on salt concentration and pH is qualitatively wrong.While using AHBC the peptide finds its native structure within 10 ns,and then fluctuates around this folded state.Under high salt concentration or extreme pH conditions the calculated helical structure probability drops,which is in qualitative agreement with the experiment.Analysis of the atomic charges and the interaction between the donor-acceptor pair in main hydrogen bonds shows that the helical structure is stabilized when polarization effect is counted.It again shows that polarization effect is a very important improvement over traditional force field and is essential for protein folding.We also prove that the salt bridge interaction between 4-residue apart GLU and LYS residues is not critical to the stability of helical structure of EK peptide,but is merely an auxiliary factor,also in agreement with the experiment.

关 键 词：EK peptide POLARIZATION salt concentration PH 

分 类 号：O641.6[理学—物理化学] TM712[理学—化学]