Molecular simulations of beta-sheet twisting.

Twisted conformations of two- and three-stranded antiparallel beta-sheet models containing alanine, glycine and valine with three or five residues per strand have been studied by molecular dynamics simulations. Free molecular dynamics and free energy simulations have been carried out to characterize the dynamics and energetics of the conformational change from a flat sheet to a twisted sheet. By altering the charges on the model in the free energy simulations, we have been able to analyze the contributions to the twist from electrostatic and van der Waals interactions. We have found that alanine and valine beta-sheets prefer conformations with a right-handed twist. In contrast, model glycine sheets do not have a pronounced preference to twist. Single beta-strands are found to be easily twisted, but to not have a strong preference for twisted conformations. Hence, the driving forces for the right-handed twist of beta-sheets must come principally from interactions between strands. These results disagree with several previous theoretical studies and constitute a different paradigm of the origin of beta-sheet twist observed in proteins.