Distance geometry generates native-like folds for small helical proteins using the consensus distances of predicted protein structures.
For successful ab initio protein structure prediction, a method is needed to identify native-like structures from a set containing both native and non-native protein-like conformations. In this regard, the use of distance geometry has shown promise when accurate inter-residue distances are available. We describe a method by which distance geometry restraints are culled from sets of 500 protein-like conformations for four small helical proteins generated by the method of Simons et al. (1997). A consensus-based approach was applied in which every inter-Calpha distance was measured, and the most frequently occurring distances were used as input restraints for distance geometry. For each protein, a structure with lower coordinate root-mean-square (RMS) error than the mean of the original set was constructed; in three cases the topology of the fold resembled that of the native protein. When the fold sets were filtered for the best scoring conformations with respect to an all-atom knowledge-based scoring function, the remaining subset of 50 structures yielded restraints of higher accuracy. A second round of distance geometry using these restraints resulted in an average coordinate RMS error of 4.38 A.
Huang
E S
ES
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
Samudrala
R
R
Ponder
J W
JW
D003198:Computer Simulation; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012097:Repressor Proteins / Q000737:chemistry; D012984:Software; D013205:Staphylococcal Protein A / Q000737:chemistry; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011506:Proteins; D012097:Repressor Proteins; D013205:Staphylococcal Protein A; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins