Ab initio protein structure prediction using a combined hierarchical approach.
As part of the third Critical Assessment of Structure Prediction meeting (CASP3), we predict the three-dimensional structures for 13 proteins using a hierarchical approach. First, all possible compact conformations of a protein sequence are enumerated using a highly simplified tetrahedral lattice model. We select a large subset of these conformations using a lattice-based scoring function and build detailed all-atom models incorporating predicted secondary structure. A combined all-atom knowledge-based scoring function is then used to select three smaller subsets from these all-atom models. Finally, a consensus-based distance geometry procedure is used to generate the best conformations from each of the all-atom subsets. With this method, we are able to predict the global topology/shape for all or a large part of the sequence for six out of the thirteen proteins. For two other proteins, the topology/shape for shorter fragments are predicted. This represents a marked improvement in ab initio prediction since CASP was first instigated in 1994.
Samudrala
R
R
Department of Structural Biology, Stanford University School of Medicine 94305, USA. ram@zen.stanford.edu
Xia
Y
Y
Huang
E
E
Levitt
M
M
D000465:Algorithms; D020407:Internet; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*
D011506:Proteins