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Computational prediction of the optimal oligomeric state for membrane‐inserted β ‐barrels of protegrin‐1 and related mutants
Author(s) -
Lipkin Richard,
Lazaridis Themis
Publication year - 2017
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2992
Subject(s) - membrane , peptide , molecular dynamics , chemistry , curvature , residue (chemistry) , antimicrobial peptides , mutant , crystallography , materials science , computational chemistry , organic chemistry , biochemistry , mathematics , geometry , gene
Protegrin‐1 is a widely studied 18‐residue β ‐hairpin antimicrobial peptide. Evidence suggests that it acts via a β ‐barrel pore formation mechanism, but the exact number of peptides comprising the pore state is unknown. 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.