Open Journal of Physical Chemistry, 2014, 4, 81-97 Published Online August 2014 in SciRes. http://www.scirp.org/journal/ojpc http://dx.doi.org/10.4236/ojpc.2014.43012 How to cite this paper: Srivastava, K.R. and Durani, S. (2014) A Stereochemically-Bent β-Hairpin: Scrutiny of Folding by Comparing a Heteropolypeptide and Cognate Oligoalanine. Open Journal of Physical Chemistry, 4, 81-97. http://dx.doi.org/10.4236/ojpc.2014.43012 A Stereochemically-Bent β-Hairpin: Scrutiny of Folding by Comparing a Heteropolypeptide and Cognate Oligoalanine Kinshuk Raj Srivastava 1,2* , Susheel Durani 2 1 Department of Physics and Astronomy, Michigan State University, East Lansing, USA 2 Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, India Email: * kinshukraj2@gmail.com Received 23 May 2014; revised 20 June 2014; accepted 17 July 2014 Copyright © 2014 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/ Abstract A poly-L β-hairpin bent stereochemically as a boat-shaped protein of mixed-L,D structure is scru- tinized 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 over D Pro 6 -Gly 7 and D Pro 6 - L Asp 7 dipeptide structures as a twelve-residue β-hairpin and bent ste- reochemically 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 CO 2 . The de- signed sequences were proven by spectroscopy and molecular dynamics to order with solvent ef- fects 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. Mo- lecular dynamics studies establish that heteropolypeptide well ordered as β-hairpin fold and cog- nate oligoalanine as an ensemble of hairpin-like folds in water. The ordering of cognate oligoala- nine 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. Keywords Protein Folding, Protein Stereochemistry, β-Hairpin, Polyalanine Model, Solvent Effects * Corresponding author.