How main-chains of proteins explore the free-energy landscape in native states

Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19708-13. doi: 10.1073/pnas.0810679105. Epub 2008 Dec 10.

Abstract

Understanding how a single native protein diffuses on its free-energy landscape is essential to understand protein kinetics and function. The dynamics of a protein is complex, with multiple relaxation times reflecting a hierarchical free-energy landscape. Using all-atom molecular dynamics simulations of an alpha/beta protein (crambin) and a beta-sheet polypeptide (BS2) in their "native" states, we demonstrate that the mean-square displacement of dihedral angles, defined by 4 successive C(alpha) atoms, increases as a power law of time, t(alpha), with an exponent alpha between 0.08 and 0.39 (alpha = 1 corresponds to Brownian diffusion), at 300 K. Residues with low exponents are located mainly in well-defined secondary elements and adopt 1 conformational substate. Residues with high exponents are found in loops/turns and chain ends and exist in multiple conformational substates, i.e., they move on multiple-minima free-energy profiles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Entropy*
  • Models, Chemical*
  • Peptides / chemistry
  • Plant Proteins / chemistry
  • Protein Folding*
  • Protein Structure, Secondary

Substances

  • Peptides
  • Plant Proteins
  • crambin protein, Crambe abyssinica