Geometric analysis characterizes molecular rigidity in generic and non-generic protein configurations

Journal article


Publication Details

Author(s): Budday D, Leyendecker S, van den Bedem H
Journal: Journal of the Mechanics and Physics of Solids
Publisher: Elsevier
Publication year: 2015
Volume: 83
Pages range: 36-47
ISSN: 0022-5096
Language: English


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.



 



 


FAU Authors / FAU Editors

Budday, Dominik
Chair of Applied Dynamics
Leyendecker, Sigrid Prof. Dr.-Ing.
Chair of Applied Dynamics


External institutions with authors

Stanford University


How to cite

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.

BibTeX: 

Last updated on 2018-11-08 at 02:24