title: Protein topology prediction through constraint-based search and the evaluation of topological folding rules.
abstract: An algorithm for predicting protein alpha/beta-sheet topologies from secondary structure and topological folding rules (constraints) has been developed and implemented in Prolog. This algorithm (CBS1) is based on constraint satisfaction and employs forward pruned breadth-first search and rotational invariance. CBS1 showed a 37-fold increase in efficiency over an exhaustive generate and test algorithm giving the same solution for a typical sheet of five strands whose topology was predicted from secondary structure with four topological folding constraints. Prolog specifications of a range of putative protein folding rules were then used to (i) replicate published protein topology predictions and (ii) validate these rules against known protein structures of nucleotide-binding domains. This demonstrated that (i) manual techniques for topology prediction can lead to non-exhaustive search and (ii) most of these protein folding principles were violated by specific proteins. Various extensions to the algorithm are discussed.
authors.affiliation: Biomedical Computing Unit, Imperial Cancer Research Fund Laboratories, London, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Clark
authors.forename: J
authors.initials: J
authors.lastname: Shirazi
authors.forename: C J
authors.initials: CJ
authors.lastname: Rawlings
mesh_terms: D000465:Algorithms; D003663:Decision Trees; D004798:Enzymes / Q000737:chemistry*; D005980:Glutathione Reductase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000737:chemistry; D008432:Mathematical Computing; D008956:Models, Chemical; D010206:Papain / Q000737:chemistry; D010732:Phosphofructokinase-1 / Q000737:chemistry; D010735:Phosphoglycerate Kinase / Q000737:chemistry; D011487:Protein Conformation; D012984:Software; D013499:Surface Properties; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry
chemical_list: D004798:Enzymes; D007770:L-Lactate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D013762:Tetrahydrofolate Dehydrogenase; D005980:Glutathione Reductase; D010732:Phosphofructokinase-1; D010735:Phosphoglycerate Kinase; D010206:Papain