Virtual Screening for Dipeptide Aggregation: Toward Predictive Tools for Peptide Self-Assembly

J Phys Chem Lett. 2011 Oct 6;2(19):2380-2384. doi: 10.1021/jz2010573. Epub 2011 Sep 2.

Abstract

Several short peptide sequences are known to self-assemble into supramolecular nanostructures with interesting properties. In this study, coarse-grained molecular dynamics is employed to rapidly screen all 400 dipeptide combinations and predict their ability to aggregate as a potential precursor to their self-assembly. The simulation protocol and scoring method proposed allows a rapid determination of whether a given peptide sequence is likely to aggregate (an indicator for the ability to self-assemble) under aqueous conditions. Systems that show strong aggregation tendencies in the initial screening are selected for longer simulations, which result in good agreement with the known self-assembly or aggregation of dipeptides reported in the literature. Our extended simulations of the diphenylalanine system show that the coarse-grain model is able to reproduce salient features of nanoscale systems and provide insight into the self-assembly process for this system.