title: Orientational potentials extracted from protein structures improve native fold recognition.
abstract: We develop coarse-grained, distance- and orientation-dependent statistical potentials from the growing protein structural databases. For protein structural classes (alpha, beta, and alpha/beta), a substantial number of backbone-backbone and backbone-side-chain contacts stabilize the native folds. By taking into account the importance of backbone interactions with a virtual backbone interaction center as the 21st anisotropic site, we construct a 21 x 21 interaction scheme. The new potentials are studied using spherical harmonics analysis (SHA) and a smooth, continuous version is constructed using spherical harmonic synthesis (SHS). Our approach has the following advantages: (1) The smooth, continuous form of the resulting potentials is more realistic and presents significant advantages for computational simulations, and (2) with SHS, the potential values can be computed efficiently for arbitrary coordinates, requiring only the knowledge of a few spherical harmonic coefficients. The performance of the new orientation-dependent potentials was tested using a standard database of decoy structures. The results show that the ability of the new orientation-dependent potentials to recognize native protein folds from a set of decoy structures is strongly enhanced by the inclusion of anisotropic backbone interaction centers. The anisotropic potentials can be used to develop realistic coarse-grained simulations of proteins, with direct applications to protein design, folding, and aggregation.
authors.affiliation: Department of Chemistry, Boston University, Boston, MA 02215, USA. straub@bu.edu
authors.forename: Nicolae-Viorel
authors.initials: NV
authors.lastname: Buchete
authors.forename: John E
authors.initials: JE
authors.lastname: Straub
authors.forename: Devarajan
authors.initials: D
authors.lastname: Thirumalai
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D019295:Computational Biology; D008956:Models, Chemical; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D011506:Proteins