TY  - JOUR
AU  - Ghaemi, Zhaleh
AU  - Minozzi, Manuela
AU  - Carloni, Paolo
AU  - Laio, Alessandro
TI  - A Novel Approach to the Investigation of Passive Molecular Permeation through Lipid Bilayers from Atomistic Simulations
JO  - The journal of physical chemistry  / B
VL  - 116
IS  - 29
SN  - 1520-5207
CY  - Washington, DC
PB  - Soc.
M1  - FZJ-2015-03600
SP  - 8714 - 8721
PY  - 2012
AB  - Predicting the permeability coefficient (P) of drugs permeating through the cell membrane is of paramount importance in drug discovery. We here propose an approach for calculating P based on bias-exchange metadynamics. The approach allows constructing from atomistic simulations a model of permeation taking explicitly into account not only the “trivial” reaction coordinate, the position of the drug along the direction normal to the lipid membrane plane, but also other degrees of freedom, for example, the torsional angles of the permeating molecule, or variables describing its solvation/desolvation. This allows deriving an accurate picture of the permeation process, and constructing a detailed molecular model of the transition state, making a rational control of permeation properties possible. We benchmarked this approach on the permeation of ethanol molecules through a POPC membrane, showing that the value of P calculated with our model agrees with the one calculated by a long unbiased molecular dynamics of the same system.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000306724100034
DO  - DOI:10.1021/jp301083h
UR  - https://juser.fz-juelich.de/record/201295
ER  -