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J Membr Biol. 2018 Jun;251(3):345-356. doi: 10.1007/s00232-018-0026-y. Epub 2018 Mar 8.

Computed Free Energies of Peptide Insertion into Bilayers are Independent of Computational Method.

Author information

1
School of Physics, Georgia Tech, Atlanta, GA, USA. gumbart@physics.gatech.edu.
2
Department of Chemistry, King's College, London, SE1 1DB, UK.
3
School of Physics, Georgia Tech, Atlanta, GA, USA.
4
Department of Physiology & Biophysics, University of California at Irvine, Irvine, CA, USA.
5
Department of Physics and the Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China. jakob@sjtu.edu.cn.

Abstract

We show that the free energy of inserting hydrophobic peptides into lipid bilayer membranes from surface-aligned to transmembrane inserted states can be reliably calculated using atomistic models. We use two entirely different computational methods: high temperature spontaneous peptide insertion calculations as well as umbrella sampling potential-of-mean-force (PMF) calculations, both yielding the same energetic profiles. The insertion free energies were calculated using two different protein and lipid force fields (OPLS protein/united-atom lipids and CHARMM36 protein/all-atom lipids) and found to be independent of the simulation parameters. In addition, the free energy of insertion is found to be independent of temperature for both force fields. However, we find major difference in the partitioning kinetics between OPLS and CHARMM36, likely due to the difference in roughness of the underlying free energy surfaces. Our results demonstrate not only a reliable method to calculate insertion free energies for peptides, but also represent a rare case where equilibrium simulations and PMF calculations can be directly compared.

KEYWORDS:

Membrane; Molecular dynamics; Peptide partitioning; Transfer free energy; Translocon

PMID:
29520628
PMCID:
PMC6030508
[Available on 2019-06-01]
DOI:
10.1007/s00232-018-0026-y

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