title: Building blocks, hinge-bending motions and protein topology.
abstract: Here we show that the locations of molecular hinges in protein structures fall between building block elements. Building blocks are fragments of the protein chain which constitute local minima. These elements fold first. In the next step they associate through a combinatorial assembly process. While chain-linked building blocks may be expected to trial-associate first, if unstable, alternate more stable associations will take place. Hence, we would expect that molecular hinges will be at such inter-building block locations, or at the less stable, unassigned regions. On the other hand, hinge-bending motions are well known to be critical for protein function. Hence, protein folding and protein function are evolutionarily related. Further, the pathways through which proteins attain their three dimensional folds are determined by protein topology. However, at the same time the locations of the hinges, and hinge-bending motions are also an outcome of protein topology. Thus, protein folding and function appear coupled, and relate to protein topology. Here we provide some results illustrating such a relationship.
authors.affiliation: Intramural Research Support Program-SAIC Laboratory of Experimental and Computational Biology, NCI-Frederick, National Institutes of Health, Bldg 469, Rm 151, Frederick, MD 21702, USA.
authors.forename: N
authors.initials: N
authors.lastname: Sinha
authors.forename: C J
authors.initials: CJ
authors.lastname: Tsa
authors.forename: R
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques; D030562:Databases, Protein; D016333:HIV Protease / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D010802:Phylogeny; D017354:Point Mutation; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D013604:T-Phages / Q000737:chemistry / Q000201:enzymology
chemical_list: D010446:Peptide Fragments; D011506:Proteins; D016333:HIV Protease