Ab initio prediction of helical segments in polypeptides.
An ab initio method has been developed to predict helix formation for polypeptides. The approach relies on the systematic analysis of overlapping oligopeptides to determine the helical propensity for individual residues. Detailed atomistic level modeling, including entropic contributions, and solvation/ionization energies calculated through the solution of the Poisson-Boltzmann equation, is utilized. The calculation of probabilities for helix formation is based on the generation of ensembles of low energy conformers. The approach, which is easily amenable to parallelization, is shown to perform very well for several benchmark polypeptide systems, including the bovine pancreatic trypsin inhibitor, the immunoglobulin binding domain of protein G, the chymotrypsin inhibitor 2, the R69 N-terminal domain of phage 434 repressor, and the wheat germ agglutinin.
Klepeis
J L
JL
Department of Chemical Engineering, Princeton University, New Jersey 08544-5263, USA.
Floudas
C A
CA
D000818:Animals; D007611:Aprotinin / Q000737:chemistry; D004268:DNA-Binding Proteins; D006801:Humans; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D010940:Plant Proteins; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry; D013816:Thermodynamics; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D014909:Wheat Germ Agglutinins / Q000737:chemistry
D004268:DNA-Binding Proteins; C029152:G-substrate; D009419:Nerve Tissue Proteins; D010455:Peptides; D010940:Plant Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D014909:Wheat Germ Agglutinins; C093336:chymotrypsin inhibitor 2; C016649:phage repressor proteins; D007611:Aprotinin