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Backbone entropy of loops as a measure of their flexibility: Application to a Ras protein simulated by molecular dynamics
- Source :
- Proteins: Structure, Function, and Bioinformatics; October 1997, Vol. 29 Issue: 2 p127-140, 14p
- Publication Year :
- 1997
-
Abstract
- The flexibility of surface loops plays an important role in proteinprotein and proteinpeptide recognition; it is commonly studied by Molecular Dynamics or Monte Carlo simulations. We propose to measure the relative backbone flexibility of loops by the difference in their backbone conformational entropies, which are calculated here with the local states (LS) method of Meirovitch. Thus, one can compare the entropies of loops of the same protein or, under certain simulation conditions, of different proteins. These loops should be equal in size but can differ in their sequence of amino acids residues. This methodology is applied successfully to three segments of 10 residues of a Ras protein simulated by the stochastic boundary molecular dynamics procedure. For the first time estimates of backbone entropy differences are obtained, and their correlation with B factors is pointed out; for example, the segments which consist of residues 6065 and 112117 have average B factors of 67 and 18 Å<SUP>2</SUP>, respectively, and entropy difference T ΔS = 5.4 ± 0.1 kcal/mol at T = 300 K. In a large number of recent publications the entropy due to the fast motions (on the ps-ns time scale) of NH and CH vectors has been obtained from their order parameter, measured in nuclear magnetic resonance spin relaxation experiments. This enables one to estimate differences in the entropy of protein segments due to foldingunfolding transitions, for example. However, the vectors are assumed to be independent, and the effect of the neglected correlations is unknown; our method is expected to become an important tool for assessing this approximation. The present calculations, obtained with the LS method, suggest that the errors involved in experimental entropy differences might not be large; however, this should be verified in each case. Potential applications of entropy calculations to rational drug design are discussed. Proteins 29:127140, 1997. © 1997 Wiley-Liss, Inc.
Details
- Language :
- English
- ISSN :
- 08873585 and 10970134
- Volume :
- 29
- Issue :
- 2
- Database :
- Supplemental Index
- Journal :
- Proteins: Structure, Function, and Bioinformatics
- Publication Type :
- Periodical
- Accession number :
- ejs1867607
- Full Text :
- https://doi.org/10.1002/(SICI)1097-0134(199710)29:2<127::AID-PROT1>3.0.CO;2-A