Refining amino acid hydrophobicity for dynamics simulation of membrane proteins
- Published
- Accepted
- Subject Areas
- Biophysics, Computational Biology, Computational Science
- Keywords
- membrane protein, molecular dynamics simulation, hydrophobicity scale, coarse-grained force field, bilayer permeation
- Copyright
- © 2017 Hills, Jr
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2017. Refining amino acid hydrophobicity for dynamics simulation of membrane proteins. PeerJ Preprints 5:e3306v1 https://doi.org/10.7287/peerj.preprints.3306v1
Abstract
Coarse-grained simulations enable the study of membrane proteins in the context of their native environment but require reliable parameters. The CgProt force field is assessed by comparing the potentials of mean force for sidechain insertion in a DOPC bilayer to results reported for atomistic molecular dynamics simulations. The reassignment of polar sidechain sites was found to improve the attractive interfacial behavior of tyrosine, phenylalanine and asparagine as well as charged lysine and arginine residues. The solvation energy at membrane depths of 0, 1.3 and 1.7 nm correlate with experimental partition coefficients in aqueous mixtures of cyclohexane, octanol and POPC, respectively, for sidechain analogs and Wimley-White peptides. These data points can be used to further discriminate between alternate force field parameters. Available partitioning data was also used to reparameterize the representation of the polar peptide backbone for non-alanine residues. The newly developed force field, CgProt 2.4, correctly predicts the global energy minimum in the potentials of mean force for insertion of the uncharged membrane-associated peptides LS3 and WALP23. CgProt will find application in molecular dynamics simulations of a variety of membrane protein systems.
Author Comment
This is a submission to PeerJ for review.
Supplemental Information
CgProt 2.4 Force Field
Version 2.4 of the CgProt force field is included as a tar.gz archive. The package includes parameter text files, Python scripts, and equilibrated bilayer coordinates needed for simulations in Gromacs.