Geometric analysis characterizes molecular rigidity in generic and non-generic protein configurations
Budday D, Leyendecker S, van den Bedem H (2015)
Publication Language: English
Publication Type: Journal article
Publication year: 2015
Journal
Publisher: Elsevier
Book Volume: 83
Pages Range: 36-47
DOI: 10.1016/j.jmps.2015.06.006
Open Access Link: http://www.ncbi.nlm.nih.gov/pubmed/26213417
Abstract
Proteins operate and interact with partners by dynamically exchanging between functional substates of a conformational ensemble on a rugged free energy landscape. Understanding how these substates are linked by coordinated, collective motions requires exploring a high-dimensional space, which remains a tremendous challenge. While molecular dynamics simulations can provide atomically detailed insight into the dynamics, computational demands to adequately sample conformational ensembles of large biomolecules and their complexes often require tremendous resources. Kinematic models can provide high-level insights into conformational ensembles and molecular rigidity beyond the reach of molecular dynamics by reducing the dimensionality of the search space. Here, we model a protein as a kinematic linkage and present a new geometric method to characterize molecular rigidity from the constraint manifold Q and its tangent space TqQ
at the current configuration q. In contrast to methods based on combinatorial constraint counting, our method is valid for both generic and non-generic, e.g., singular configurations. Importantly, our geometric approach provides an explicit basis for collective motions along floppy modes, resulting in an efficient procedure to probe conformational space. An atomically detailed structural characterization of coordinated, collective motions would allow us to engineer or allosterically modulate biomolecules by selectively stabilizing conformations that enhance or inhibit function with broad implications for human health.
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APA:
Budday, D., Leyendecker, S., & van den Bedem, H. (2015). Geometric analysis characterizes molecular rigidity in generic and non-generic protein configurations. Journal of the Mechanics and Physics of Solids, 83, 36-47. https://dx.doi.org/10.1016/j.jmps.2015.06.006
MLA:
Budday, Dominik, Sigrid Leyendecker, and Henry van den Bedem. "Geometric analysis characterizes molecular rigidity in generic and non-generic protein configurations." Journal of the Mechanics and Physics of Solids 83 (2015): 36-47.
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