A Stereochemically-Bent <i>β</i>-Hairpin: Scrutiny of Folding by Comparing a Heteropolypeptide and Cognate Oligoalanine

作     者：Kinshuk Raj Srivastava Susheel Durani 

作者机构：Department of Chemistry Indian Institute of Technology Bombay Mumbai India Department of Physics and Astronomy Michigan State University East Lansing USA 

出 版 物：《Open Journal of Physical Chemistry》 (物理化学期刊（英文）)

年 卷 期：2014年第4卷第3期

页      面：81-97页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Protein Folding Protein Stereochemistry β-Hairpin Polyalanine Model Solvent Effects 

摘      要：A poly-L β-hairpin bent stereochemically as a boat-shaped protein of mixed-L,D structure is scrutinized in basis of ordering as minimum of energy specific for its sequenceand solvent. The model suitable for the scrutiny is accomplished by design. A terminally-blocked oligoalanine is nucleated overDPro6-Gly7 and DPro6-LAsp7 dipeptide structures as a twelve-residue β-hairpin and bent stereochemically as a boat-shaped fold. The structure is inverse designed with side chains suitable to bind substrate p-nitophenyl phosphate, a surrogate substrate of acetyl choline and CO2. The designed sequences were proven by spectroscopy and molecular dynamics to order with solvent effects of water and display high binding affinity for the substrate. One of the proteins and a cognate oligoalanine are evolved with molecular dynamics to equilibrium in a solvent bath of water. Molecular dynamics studies establish that heteropolypeptide well ordered as β-hairpin fold and cognate oligoalanine as an ensemble of hairpin-like folds in water. The ordering of cognate oligoalanine as ensembles of hairpin-like folds manifests combined role of water as strong dielectric and weak dipolar solvent of peptides. The roles of stereochemistry and chemical details of sequence in defining polypeptides as energy minima under specific effect of solvent are illuminated and have been discussed.