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) |
|---|---|
| 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 |
Fingerprint
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
Cite this
Refining the treatment of membrane proteins by coarse-grained models. / Vorobyov, Igor; Kim, Ilsoo; Chu, Zhen T.; Warshel, Arieh.
In: Proteins: Structure, Function and Bioinformatics, Vol. 84, No. 1, 01.01.2016, p. 92-117.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Refining the treatment of membrane proteins by coarse-grained models
AU - Vorobyov, Igor
AU - Kim, Ilsoo
AU - Chu, Zhen T.
AU - Warshel, Arieh
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Arginine
KW - Folding energy
KW - Ion-induced defect
KW - Lipid membrane
KW - Membrane electrostatics
KW - Molecular modeling
KW - Mutation
KW - OmpLA
KW - Partitioning free energy
KW - Rotamer
UR - http://www.scopus.com/inward/record.url?scp=84954375280&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84954375280&partnerID=8YFLogxK
U2 - 10.1002/prot.24958
DO - 10.1002/prot.24958
M3 - Article
VL - 84
SP - 92
EP - 117
JO - Proteins: Structure, Function and Bioinformatics
JF - Proteins: Structure, Function and Bioinformatics
SN - 0887-3585
IS - 1
ER -