Conformational structure, dynamics, and solvation energies of small alanine peptides in water and carbon tetrachloride

Journal of Pharmaceutical Sciences
Tian-Xiang Xiang, Bradley D Anderson

Abstract

The rate-limiting barrier for peptide transport across lipid bilayers is the nonpolar hydrocarbon interior. Permeating peptides may undergo conformational changes during their transfer from an aqueous solution into the barrier domain, thus facilitating peptide transport. To test this hypothesis, all-atom and explicit-solvent molecular dynamics (MD) simulations have been conducted on a series of small peptides, p-toluyl-Ala(n) (n = 0-3) used previously in transport experiments, to explore their conformational structures, dynamics and solvation free energies in water and carbon tetrachloride (CCl(4)). The conformations of the p-toluyl alanine di- and tri-peptides in water were found to be far from random coils, with P(II) and alpha(R) dominating but with smaller populations of seven-membered (c(7)) and five-membered rings (c(5)). In contrast, the seven-membered ring, c(7), along with c(5) dominated in CCl(4). These results indicate that the conformational preferences of the alanine peptides are highly sensitive to solvent. Dynamically, stable seven-membered ring formation occurred on a time scale of 10 ps while larger ring-sizes (e.g., 10-membered rings) were observed much less frequently. The values of adjacent torsional angles ...Continue Reading

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Citations

May 20, 2008·Journal of Molecular Graphics & Modelling·Alik S WidgeMaria Kurnikova
Nov 10, 2006·Advanced Drug Delivery Reviews·Tian-Xiang Xiang, Bradley D Anderson
Mar 18, 2011·Physical Chemistry Chemical Physics : PCCP·Christophe DéjugnatThomas Zemb
Jun 26, 2007·The Journal of Physical Chemistry. a·Jennifer A GoodnoughThomas C Farrar
Apr 15, 2011·Journal of Pharmaceutical Sciences·Yong Cui

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