A restraint molecular dynamics and simulated annealing approach for protein homology modeling utilizing mean angles.
BACKGROUND
We have developed the program PERMOL for semi-automated homology modeling of proteins. It is based on restrained molecular dynamics using a simulated annealing protocol in torsion angle space. As main restraints defining the optimal local geometry of the structure weighted mean dihedral angles and their standard deviations are used which are calculated with an algorithm described earlier by Doker et al. (1999, BBRC, 257, 348-350). The overall long-range contacts are established via a small number of distance restraints between atoms involved in hydrogen bonds and backbone atoms of conserved residues. Employing the restraints generated by PERMOL three-dimensional structures are obtained using standard molecular dynamics programs such as DYANA or CNS.


RESULTS
To test this modeling approach it has been used for predicting the structure of the histidine-containing phosphocarrier protein HPr from E. coli and the structure of the human peroxisome proliferator activated receptor gamma (Ppar gamma). The divergence between the modeled HPr and the previously determined X-ray structure was comparable to the divergence between the X-ray structure and the published NMR structure. The modeled structure of Ppar gamma was also very close to the previously solved X-ray structure with an RMSD of 0.262 nm for the backbone atoms.


CONCLUSIONS
In summary, we present a new method for homology modeling capable of producing high-quality structure models. An advantage of the method is that it can be used in combination with incomplete NMR data to obtain reasonable structure models in accordance with the experimental data.
Möglich
Andreas
A
Institut für Biophysik und physikalische Biochemie, Universität Regensburg, Universitätsstr. 31, D-93053 Regensburg, Germany. andreas.moeglich@unibas.ch
Weinfurtner
Daniel
D
Maurer
Till
T
Gronwald
Wolfram
W
Kalbitzer
Hans Robert
HR
D000465:Algorithms; D001426:Bacterial Proteins / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D003196:Computer Graphics; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D013293:Enterococcus faecalis / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D008962:Models, Theoretical; D008968:Molecular Conformation; D047495:PPAR gamma / Q000235:genetics; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D020539:Sequence Analysis, Protein; D012984:Software
D001426:Bacterial Proteins; D047495:PPAR gamma; D006639:Histidine; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C030182:phosphocarrier protein HPr