Mapping the free-energy landscape of trans-membrane pores by atomistic molecular dynamics simulations

NORA A. E. MOYANO; JOAQUÍN KLUG; CARLES TRIGUERO; GARETH A. TRIBELLO; NIALL ENGLISH; VANESA GALASSI; JORGE J. KOHANOFF; DANIEL MILLÁN; MARIO G. DEL PÓPOLO

Dublin

Workshop; Computer Simulation of Chemical Technologies involving Confined Liquids; 2018

University College Dublin

When lipid membranes are submitted to mechanical or electrical stress, the formation of pores and water channels leads to concomitant changes in water permeability and ionic conductivity. Moreover, the energetic cost of creating transmembrane defects is a determining factor in physiological processes at the cellular level and affects, among other things, the transport of drugs and metabolites through the lipid bilayer. In the present work, we resort to 2D meta-dynamics simulations to produce a free-energy map that allows to identify the formation energy and nucleation mechanism of transmembrane pores with different sizes and levels of hydration. We make use of two complementary collective variables: one controls the lipid density around a specified point on the membrane plane, and thus allows to create a pore, and the other controls the number of water molecules inside the pore. We present preliminary results for an atomistic POPC bilayer that include, for example, the formation of percolating water wires across the bilayer.