Abstract
The distance constraint model (DCM) is a unique computational modeling paradigm that integrates mechanical and thermodynamic descriptions of macromolecular structure. That is, network rigidity calculations are used to account for nonadditivity within entropy components, thus restoring the utility of free-energy decomposition. The DCM outputs a large number of structural characterizations that collectively allow for quantified stability–flexibility relationships (QSFR) to be identified. In this review, we describe the theoretical underpinnings of the DCM and introduce several common QSFR metrics. Application of the DCM across protein families highlights the sensitivity within the set of protein structure residue-to-residue couplings. Further, we have developed a perturbation method to identify putative allosteric sites, where large changes in QSFR upon rigidification (mimicking ligand-binding) detect sites likely to invoke allosteric changes.
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Acknowledgement
The work described here has been primarily supported by the NIH since 2003. We acknowledge continuing support from NIH NIGMS grant R01 GM073082, which is allowing us to extend these ideas more fully.
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Jacobs, D.J., Livesay, D.R., Mottonen, J.M., Vorov, O.K., Istomin, A.Y., Verma, D. (2012). Ensemble Properties of Network Rigidity Reveal Allosteric Mechanisms. In: Fenton, A. (eds) Allostery. Methods in Molecular Biology, vol 796. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-334-9_15
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DOI: https://doi.org/10.1007/978-1-61779-334-9_15
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