title: General trends of dihedral conformational transitions in a globular protein.
abstract: Dihedral conformational transitions are analyzed systematically in a model globular protein, cytochrome P450cam, to examine their structural and chemical dependences through combined conventional molecular dynamics (cMD), accelerated molecular dynamics (aMD) and adaptive biasing force (ABF) simulations. The aMD simulations are performed at two acceleration levels, using dihedral and dual boost, respectively. In comparison with cMD, aMD samples protein dihedral transitions approximately two times faster on average using dihedral boost, and ∼ 3.5 times faster using dual boost. In the protein backbone, significantly higher dihedral transition rates are observed in the bend, coil, and turn flexible regions, followed by the β bridge and β sheet, and then the helices. Moreover, protein side chains of greater length exhibit higher transition rates on average in the aMD-enhanced sampling. Side chains of the same length (particularly Nχ = 2) exhibit decreasing transition rates with residues when going from hydrophobic to polar, then charged and aromatic chemical types. The reduction of dihedral transition rates is found to be correlated with increasing energy barriers as identified through ABF free energy calculations. These general trends of dihedral conformational transitions provide important insights into the hierarchical dynamics and complex free energy landscapes of functional proteins.
authors.affiliation: Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California, 92093.|Department of Pharmacology, University of California at San Diego, La Jolla, California, 92093.
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Miao
authors.affiliation: University of Tennessee/Oak Ridge National Laboratory Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee, 37831.|Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee, 37996.
authors.forename: Jerome
authors.initials: J
authors.lastname: Baudry
authors.affiliation: University of Tennessee/Oak Ridge National Laboratory Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee, 37831.|Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee, 37996.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Smith
authors.affiliation: Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California, 92093.|Department of Pharmacology, University of California at San Diego, La Jolla, California, 92093.|Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California, 92093.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D000072417:Protein Domains; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016958:Pseudomonas putida / Q000737:chemistry* / Q000201:enzymology; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D003577:Cytochrome P-450 Enzyme System
keywords: dihedral conformational transitions; enhanced sampling; free energy; globular protein; molecular dynamics