TY - JOUR
T1 - Prediction of protein side-chain rotamers from a backbone-dependent rotamer library
T2 - A new homology modeling tool
AU - Bower, Michael J.
AU - Cohen, Fred E.
AU - Dunbrack, Roland L.
PY - 1997/4/18
Y1 - 1997/4/18
N2 - Modeling by homology is the most accurate computational method for translating an amino acid sequence into a protein structure. Homology modeling can be divided into two sub-problems, placing the polypeptide backbone and adding side-chains. We present a method for rapidly predicting the conformations of protein side-chains, starting from main-chain coordinates alone. The method involves using fewer than ten rotamers per residue from a backbone-dependent rotamer library and a search to remove steric;conflicts. The method is initially tested on 299 high resolution crystal structures by rebuilding side-chains onto the experimentally determined backbone structures. A total of 77% of χ1 and 66% of χ1+2 dihedral angles are predicted within 40°of their crystal structure values. We then tested the method on the entire database of known structures in the Protein Data Bank. The predictive accuracy of the algorithm was strongly correlated with the resolution of the structures. In an effort to simulate a realistic homology modeling problem, 9424 homology models were created using three different modeling strategies. For prediction purposes, pairs of structures were identified which shared between 30% and 90% sequence identity. One strategy results in 82% of χ1 and 72% χ1+2 dihedral angles predicted within 40 degrees of the target crystal structure values, suggesting that movements of the backbone associated with this degree of sequence identity are not large enough to disrupt the predictive ability of our method for non-native backbones. These results compared favorably with existing methods over a comprehensive data set.
AB - Modeling by homology is the most accurate computational method for translating an amino acid sequence into a protein structure. Homology modeling can be divided into two sub-problems, placing the polypeptide backbone and adding side-chains. We present a method for rapidly predicting the conformations of protein side-chains, starting from main-chain coordinates alone. The method involves using fewer than ten rotamers per residue from a backbone-dependent rotamer library and a search to remove steric;conflicts. The method is initially tested on 299 high resolution crystal structures by rebuilding side-chains onto the experimentally determined backbone structures. A total of 77% of χ1 and 66% of χ1+2 dihedral angles are predicted within 40°of their crystal structure values. We then tested the method on the entire database of known structures in the Protein Data Bank. The predictive accuracy of the algorithm was strongly correlated with the resolution of the structures. In an effort to simulate a realistic homology modeling problem, 9424 homology models were created using three different modeling strategies. For prediction purposes, pairs of structures were identified which shared between 30% and 90% sequence identity. One strategy results in 82% of χ1 and 72% χ1+2 dihedral angles predicted within 40 degrees of the target crystal structure values, suggesting that movements of the backbone associated with this degree of sequence identity are not large enough to disrupt the predictive ability of our method for non-native backbones. These results compared favorably with existing methods over a comprehensive data set.
KW - Algorithms
KW - Amino Acids/chemistry
KW - Computer Simulation
KW - Databases, Factual
KW - Models, Molecular
KW - Protein Conformation
KW - Reproducibility of Results
KW - Sequence Homology, Amino Acid
UR - http://www.scopus.com/inward/record.url?scp=0031576989&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:A1997WU94200017&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1006/jmbi.1997.0926
DO - 10.1006/jmbi.1997.0926
M3 - Article
C2 - 9150411
SN - 0022-2836
VL - 267
SP - 1268
EP - 1282
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 5
ER -