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Title: General trends of dihedral conformational transitions in a globular protein

In this paper, 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. In conclusion, these general trends of dihedral conformational transitions provide important insights into the hierarchical dynamics and complex free energy landscapes of functionalmore » proteins.« less
 [1] ;  [2] ;  [2] ;  [3]
  1. University of California at San Diego, La Jolla, CA (United States). Howard Hughes Medical Institute and Department of Pharmacology
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Molecular Biophysics; Univ. of Tennessee, Knoxville, TN (United States). Department of Biochemistry and Cellular and Molecular Biology
  3. University of California at San Diego, La Jolla, CA (United States). Howard Hughes Medical Institute, Department of Pharmacology, and Department of Chemistry and Biochemistry
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Accepted Manuscript
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Additional Journal Information:
Journal Volume: 84; Journal Issue: 4; Journal ID: ISSN 0887-3585
Research Org:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
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Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; dihedral conformational transitions; molecular dynamics; enhanced sampling; free energy; globular protein
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