Ab initio protein structure prediction using a combined hierarchical approach

✍ Scribed by Ram Samudrala; Yu Xia; Enoch Huang; Michael Levitt

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 169 KB
• Volume: 37
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/(sici)1097-0134(1999)37:3+<194::aid-prot24>3.0.co;2-f

✦ Synopsis

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 allatom 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.