Advanced

Energy Fluctuations Shape Free Energy of Nonspecific Biomolecular Interactions

Elkin, Michael; André, Ingemar LU and Lukatsky, David B. (2012) In Journal of Statistical Physics 146(4). p.870-877
Abstract
Understanding design principles of biomolecular recognition is a key question of molecular biology. Yet the enormous complexity and diversity of biological molecules hamper the efforts to gain a predictive ability for the free energy of protein-protein, protein-DNA, and protein-RNA binding. Here, using a variant of the Derrida model, we predict that for a large class of biomolecular interactions, it is possible to accurately estimate the relative free energy of binding based on the fluctuation properties of their energy spectra, even if a finite number of the energy levels is known. We show that the free energy of the system possessing a wider binding energy spectrum is almost surely lower compared with the system possessing a narrower... (More)
Understanding design principles of biomolecular recognition is a key question of molecular biology. Yet the enormous complexity and diversity of biological molecules hamper the efforts to gain a predictive ability for the free energy of protein-protein, protein-DNA, and protein-RNA binding. Here, using a variant of the Derrida model, we predict that for a large class of biomolecular interactions, it is possible to accurately estimate the relative free energy of binding based on the fluctuation properties of their energy spectra, even if a finite number of the energy levels is known. We show that the free energy of the system possessing a wider binding energy spectrum is almost surely lower compared with the system possessing a narrower energy spectrum. Our predictions imply that low-affinity binding scores, usually wasted in protein-protein and protein-DNA docking algorithms, can be efficiently utilized to compute the free energy. Using the results of Rosetta docking simulations of protein-protein interactions from Andre et al. (Proc. Natl. Acad. Sci. USA 105: 16148, 2008), we demonstrate the power of our predictions. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Free energy of biomolecular interactions, Fluctuations
in
Journal of Statistical Physics
volume
146
issue
4
pages
870 - 877
publisher
Springer
external identifiers
  • wos:000301730400012
  • scopus:84858333449
ISSN
1572-9613
DOI
10.1007/s10955-012-0421-1
language
English
LU publication?
yes
id
10328500-9961-4adf-b28d-0a48868e011a (old id 2515245)
date added to LUP
2012-05-15 15:29:59
date last changed
2017-01-01 06:16:13
@article{10328500-9961-4adf-b28d-0a48868e011a,
  abstract     = {Understanding design principles of biomolecular recognition is a key question of molecular biology. Yet the enormous complexity and diversity of biological molecules hamper the efforts to gain a predictive ability for the free energy of protein-protein, protein-DNA, and protein-RNA binding. Here, using a variant of the Derrida model, we predict that for a large class of biomolecular interactions, it is possible to accurately estimate the relative free energy of binding based on the fluctuation properties of their energy spectra, even if a finite number of the energy levels is known. We show that the free energy of the system possessing a wider binding energy spectrum is almost surely lower compared with the system possessing a narrower energy spectrum. Our predictions imply that low-affinity binding scores, usually wasted in protein-protein and protein-DNA docking algorithms, can be efficiently utilized to compute the free energy. Using the results of Rosetta docking simulations of protein-protein interactions from Andre et al. (Proc. Natl. Acad. Sci. USA 105: 16148, 2008), we demonstrate the power of our predictions.},
  author       = {Elkin, Michael and André, Ingemar and Lukatsky, David B.},
  issn         = {1572-9613},
  keyword      = {Free energy of biomolecular interactions,Fluctuations},
  language     = {eng},
  number       = {4},
  pages        = {870--877},
  publisher    = {Springer},
  series       = {Journal of Statistical Physics},
  title        = {Energy Fluctuations Shape Free Energy of Nonspecific Biomolecular Interactions},
  url          = {http://dx.doi.org/10.1007/s10955-012-0421-1},
  volume       = {146},
  year         = {2012},
}