Journal Article

FZJ-2015-03600

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Novel Approach to the Investigation of Passive Molecular Permeation through Lipid Bilayers from Atomistic Simulations

Ghaemi, Z. ; Minozzi, M. ; Carloni, P.FZJ* ; Laio, A. (Corresponding Author)

2012
Soc. Washington, DC

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Please use a persistent id in citations: doi:10.1021/jp301083h

Abstract: 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.

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Contributing Institute(s):

1. GRS (GRS)
2. Computational Biomedicine (IAS-5)

Research Program(s):

1. 899 - ohne Topic (POF2-899) (POF2-899)

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Database coverage:
; Current Contents - Physical, Chemical and Earth Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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