High-resolution protein folding with a transferable potential.
A generalized computational method for folding proteins with a fully transferable potential and geometrically realistic all-atom model is presented and tested on seven helix bundle proteins. The protocol, which includes graph-theoretical analysis of the ensemble of resulting folded conformations, was systematically applied and consistently produced structure predictions of approximately 3 A without any knowledge of the native state. To measure and understand the significance of the results, extensive control simulations were conducted. Graph theoretic analysis provides a means for systematically identifying the native fold and provides physical insight, conceptually linking the results to modern theoretical views of protein folding. In addition to presenting a method for prediction of structure and folding mechanism, our model suggests that an accurate all-atom amino acid representation coupled with a physically reasonable atomic interaction potential and hydrogen bonding are essential features for a realistic protein model.
Hubner
Isaac A
IA
Departments of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Deeds
Eric J
EJ
Shakhnovich
Eugene I
EI
D000818:Animals; D019295:Computational Biology; D003198:Computer Simulation; D030562:Databases, Protein; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009010:Monte Carlo Method; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013211:Staphylococcus aureus / Q000378:metabolism; D013291:Streptococcus / Q000378:metabolism
D011506:Proteins