title: Restriction versus guidance in protein structure prediction.
abstract: Conformational restriction by fragment assembly and guidance in molecular dynamics are alternate conformational search strategies in protein structure prediction. We examine both approaches using a version of the associative memory Hamiltonian that incorporates the influence of water-mediated interactions (AMW). For short proteins (<70 residues), fragment assembly, while searching a restricted space, compares well to molecular dynamics and is often sufficient to fold such proteins to near-native conformations (4A) via simulated annealing. Longer proteins encounter kinetic sampling limitations in fragment assembly not seen in molecular dynamics which generally samples more native-like conformations. We also present a fragment enriched version of the standard AMW energy function, AMW-FME, which incorporates the local sequence alignment derived fragment libraries from fragment assembly directly into the energy function. This energy function, in which fragment information acts as a guide not a restriction, is found by molecular dynamics to improve on both previous approaches.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093-0365, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hegler
authors.forename: Joachim
authors.initials: J
authors.lastname: Lätzer
authors.forename: Amarda
authors.initials: A
authors.lastname: Shehu
authors.forename: Cecilia
authors.initials: C
authors.lastname: Clementi
authors.forename: Peter G
authors.initials: PG
authors.lastname: Wolynes
mesh_terms: D019295:Computational Biology / Q000379:methods*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins
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