Abstract
Obtaining a quantitative description of the membrane proteins stability is crucial for understanding many biological processes. However the advance in this direction has remained a major challenge for both experimental studies and molecular modeling. One of the possible directions is the use of coarse-grained models but such models must be carefully calibrated and validated. Here we use a recent progress in benchmark studies on the energetics of amino acid residue and peptide membrane insertion and membrane protein stability in refining our previously developed coarse-grained model (Vicatos et al., Proteins 2014;82:1168). Our refined model parameters were fitted and/or tested to reproduce water/membrane partitioning energetics of amino acid side chains and a couple of model peptides. This new model provides a reasonable agreement with experiment for absolute folding free energies of several β-barrel membrane proteins as well as effects of point mutations on a relative stability for one of those proteins, OmpLA. The consideration and ranking of different rotameric states for a mutated residue was found to be essential to achieve satisfactory agreement with the reference data.
Original language | English (US) |
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Pages (from-to) | 92-117 |
Number of pages | 26 |
Journal | Proteins: Structure, Function and Bioinformatics |
Volume | 84 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2016 |
Externally published | Yes |
Keywords
- Arginine
- Folding energy
- Ion-induced defect
- Lipid membrane
- Membrane electrostatics
- Molecular modeling
- Mutation
- OmpLA
- Partitioning free energy
- Rotamer
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Molecular Biology