Computational prediction of the optimal oligomeric state for membrane ‐inserted β‐barrels of protegrin‐1 and related mutants

In this study, we performed molecular dynamics simulations of β‐barrels of protegrin and three related mutants (v14v16l, v14v16a, and r4n) in NCNC parallel topology in implicit membrane pores of varying radius and curvature for oligomeric numbers 6–14. We then identified the optimal pore radius and curvature values for all constructs and determined the total effective energy and the translational and rotational entropic losses. These, along with an estimate of membrane deformation free energy from experimental line tension values, provided an estimate of the overall energetics of formation of each pore state. The results indicated that oligomeric numbers 7–13 are generally stable, allowing the possibility of a heterogeneous pore state. The optimal oligomeric state for protegrin is the nonamer, shifting to higher numbers for the mutants. Protegrin, v14v16l, and r4n are stable as membrane‐inserted β‐barrels, but v14v16a seems much less so because of its decreased hydrophobicity. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Molecular dynamics simulations in implicit membrane pores with translational and rotational entropy estimates are used to predict the optimal oligomeric number, pore radius, and pore curvature for transmembrane β‐barrels of several analogs of the β‐hairpin antimicrobial peptide protegrin.

Source: Journal of Peptide Science - April 6, 2017 Category: Biochemistry Authors: Richard Lipkin, Themis Lazaridis Tags: Special Issue Article Source Type: research