title: A monte carlo method for generating side chain structural ensembles.
abstract: We report a Monte Carlo side chain entropy (MC-SCE) method that uses a physical energy function inclusive of long-range electrostatics and hydrophobic potential of mean force, coupled with both backbone variations and a backbone dependent side chain rotamer library, to describe protein conformational ensembles. Using the MC-SCE method in conjunction with backbone variability, we can reliably determine the side chain rotamer populations derived from both room temperature and cryogenically cooled X-ray crystallographic structures for CypA and H-Ras and NMR J-coupling constants for CypA, Eglin-C, and the DHFR product binary complexes E:THF and E:FOL. Furthermore, we obtain near perfect discrimination between a protein's native state ensemble and ensembles of misfolded structures for 55 different proteins, thereby generating far more competitive side chain packings for all of these proteins and their misfolded states.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Asmit
authors.initials: A
authors.lastname: Bhowmick
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemistry, University of California Berkeley, Berkeley, CA 94720, USA; Department of Bioengineering, University of California Berkeley, Berkeley, CA 94720, USA; Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: thg@berkeley.edu.
authors.forename: Teresa
authors.initials: T
authors.lastname: Head-Gordon
mesh_terms: D019943:Amino Acid Substitution; D018360:Crystallography, X-Ray; D017936:Cytochrome a Group / Q000737:chemistry / Q000235:genetics; D019277:Entropy; D006801:Humans; D008958:Models, Molecular; D009010:Monte Carlo Method; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000235:genetics; D013816:Thermodynamics
chemical_list: D017936:Cytochrome a Group; D011506:Proteins; C028656:eglin proteinase inhibitors; D013762:Tetrahydrofolate Dehydrogenase; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)