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The Dynameomics Entropy Dictionary : A Large-Scale Assessment of Conformational Entropy across Protein Fold Space

Towse, Clare Louise; Akke, Mikael LU and Daggett, Valerie (2017) In Journal of Physical Chemistry B 121(16). p.3933-3945
Abstract

Molecular dynamics (MD) simulations contain considerable information with regard to the motions and fluctuations of a protein, the magnitude of which can be used to estimate conformational entropy. Here we survey conformational entropy across protein fold space using the Dynameomics database, which represents the largest existing data set of protein MD simulations for representatives of essentially all known protein folds. We provide an overview of MD-derived entropies accounting for all possible degrees of dihedral freedom on an unprecedented scale. Although different side chains might be expected to impose varying restrictions on the conformational space that the backbone can sample, we found that the backbone entropy and side chain... (More)

Molecular dynamics (MD) simulations contain considerable information with regard to the motions and fluctuations of a protein, the magnitude of which can be used to estimate conformational entropy. Here we survey conformational entropy across protein fold space using the Dynameomics database, which represents the largest existing data set of protein MD simulations for representatives of essentially all known protein folds. We provide an overview of MD-derived entropies accounting for all possible degrees of dihedral freedom on an unprecedented scale. Although different side chains might be expected to impose varying restrictions on the conformational space that the backbone can sample, we found that the backbone entropy and side chain size are not strictly coupled. An outcome of these analyses is the Dynameomics Entropy Dictionary, the contents of which have been compared with entropies derived by other theoretical approaches and experiment. As might be expected, the conformational entropies scale linearly with the number of residues, demonstrating that conformational entropy is an extensive property of proteins. The calculated conformational entropies of folding agree well with previous estimates. Detailed analysis of specific cases identifies deviations in conformational entropy from the average values that highlight how conformational entropy varies with sequence, secondary structure, and tertiary fold. Notably, α-helices have lower entropy on average than do β-sheets, and both are lower than coil regions.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Physical Chemistry B
volume
121
issue
16
pages
13 pages
publisher
The American Chemical Society
external identifiers
  • scopus:85020229786
  • wos:000400534200004
ISSN
1520-6106
DOI
10.1021/acs.jpcb.7b00577
language
English
LU publication?
yes
id
12eea37e-daa9-4b61-a5b8-fa7f699130fd
date added to LUP
2017-06-28 15:36:05
date last changed
2017-09-18 11:43:36
@article{12eea37e-daa9-4b61-a5b8-fa7f699130fd,
  abstract     = {<p>Molecular dynamics (MD) simulations contain considerable information with regard to the motions and fluctuations of a protein, the magnitude of which can be used to estimate conformational entropy. Here we survey conformational entropy across protein fold space using the Dynameomics database, which represents the largest existing data set of protein MD simulations for representatives of essentially all known protein folds. We provide an overview of MD-derived entropies accounting for all possible degrees of dihedral freedom on an unprecedented scale. Although different side chains might be expected to impose varying restrictions on the conformational space that the backbone can sample, we found that the backbone entropy and side chain size are not strictly coupled. An outcome of these analyses is the Dynameomics Entropy Dictionary, the contents of which have been compared with entropies derived by other theoretical approaches and experiment. As might be expected, the conformational entropies scale linearly with the number of residues, demonstrating that conformational entropy is an extensive property of proteins. The calculated conformational entropies of folding agree well with previous estimates. Detailed analysis of specific cases identifies deviations in conformational entropy from the average values that highlight how conformational entropy varies with sequence, secondary structure, and tertiary fold. Notably, α-helices have lower entropy on average than do β-sheets, and both are lower than coil regions.</p>},
  author       = {Towse, Clare Louise and Akke, Mikael and Daggett, Valerie},
  issn         = {1520-6106},
  language     = {eng},
  month        = {04},
  number       = {16},
  pages        = {3933--3945},
  publisher    = {The American Chemical Society},
  series       = {Journal of Physical Chemistry B},
  title        = {The Dynameomics Entropy Dictionary : A Large-Scale Assessment of Conformational Entropy across Protein Fold Space},
  url          = {http://dx.doi.org/10.1021/acs.jpcb.7b00577},
  volume       = {121},
  year         = {2017},
}