Understanding Periperal Membrane Protein Interactions | BPS Thematic Meeting

Understanding Peripheral Membrane Protein Interactions: Structure, Dynamics, Function and Therapy

Poster Abstracts

6-POS Board 6 PATH SAMPLING SIMULATIONS WITH INFINITE TRAJECTORY SWAPS REVEAL THE PERMEATION KINETICS AND MECHANISM OF AMINO ACIDS An Ghysels 1 ; 1 Ghent University, IBiTech - BioMMedA group, Ghent, Belgium The interaction of amino acids with phospholipid molecules is the basis for the behavior of peripheral membrane proteins. In this study, the permeation events of amino acids and peptides are investigated using molecular dynamics simulations. As membranes form a barrier, the permeation is a rare and slow event, often beyond the timescale of what modern-day computational infrastructure can reach. Recently, a new algorithm has been developed for replica exchange transition interface sampling (RETIS), which is a Monte Carlo algorithm that samples numerous permeant trajectories. The new algorithm promotes faster decorrelation between the sampled trajectories by extending the number of exchanges to infinity (infRETIS). Using the test case of 5-aminolevulinic acid (5-ALA), we show how the advanced infRETIS methodology provides hundreds of unbiased and representative transition trajectories. Further analysis of those trajectories yields the permeability of 5-ALA. Moreover, the trajectories shed light on the permeation mechanism, for example showing that individual water molecules intrude on average less deeply into the hydrophobic membrane core in successful permeation events compared to unsuccessful attempts. The infRETIS methodology is thus a powerful tool to create unbiased trajectories of peptides interacting with the membrane, even when the timescale is prohibitively long for standard MD.

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