General trends of dihedral conformational transitions in a globular protein

Miao, Yinglong; Baudry, Jerome; Smith, Jeremy C.; McCammon, J. Andrew

doi:10.1002/prot.24996

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

Journal Article · Mon Feb 15 00:00:00 EST 2016 · Proteins

DOI:https://doi.org/10.1002/prot.24996· OSTI ID:1327620

Miao, Yinglong ^[1]; Baudry, Jerome ^[2]; Smith, Jeremy C. ^[2]; McCammon, J. Andrew ^[3]

University of California at San Diego, La Jolla, CA (United States). Howard Hughes Medical Institute and Department of Pharmacology
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
University of California at San Diego, La Jolla, CA (United States). Howard Hughes Medical Institute, Department of Pharmacology, and Department of Chemistry and Biochemistry

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 functional proteins.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1327620

Journal Information:: Proteins, Vol. 84, Issue 4; ISSN 0887-3585

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 8 works

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