title: Reducing the computational complexity of protein folding via fragment folding and assembly.
abstract: Understanding, and ultimately predicting, how a 1-D protein chain reaches its native 3-D fold has been one of the most challenging problems during the last few decades. Data increasingly indicate that protein folding is a hierarchical process. Hence, the question arises as to whether we can use the hierarchical concept to reduce the practically intractable computational times. For such a scheme to work, the first step is to cut the protein sequence into fragments that form local minima on the polypeptide chain. The conformations of such fragments in solution are likely to be similar to those when the fragments are embedded in the native fold, although alternate conformations may be favored during the mutual stabilization in the combinatorial assembly process. Two elements are needed for such cutting: (1) a library of (clustered) fragments derived from known protein structures and (2) an assignment algorithm that selects optimal combinations to "cover" the protein sequence. The next two steps in hierarchical folding schemes, not addressed here, are the combinatorial assembly of the fragments and finally, optimization of the obtained conformations. Here, we address the first step in a hierarchical protein-folding scheme. The input is a target protein sequence and a library of fragments created by clustering building blocks that were generated by cutting all protein structures. The output is a set of cutout fragments. We briefly outline a graph theoretic algorithm that automatically assigns building blocks to the target sequence, and we describe a sample of the results we have obtained.
authors.affiliation: Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Nurit
authors.initials: N
authors.lastname: Haspel
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Tsai
authors.forename: Haim
authors.initials: H
authors.lastname: Wolfson
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D019992:Databases as Topic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D016415:Sequence Alignment / Q000379:methods
chemical_list: D000596:Amino Acids; D010446:Peptide Fragments