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Thermodynamic and Kinetic Characterization of Protein Conformational Dynamics within a Riemannian Diffusion Formalism

Goolsby, C.; Fakharzadeh, A.; Moradi, M.

2019-07-26 biophysics
10.1101/707711 bioRxiv
Show abstract

We have formulated a Riemannian framework for describing the geometry of collective variable spaces of biomolecules within the context of collective variable based molecular dynamics simulations. The formalism provides a theoretical framework to develop enhanced sampling techniques, path-finding algorithms, and transition rate estimators consistent with a Riemannian treatment of the collective variable space, where the quantities of interest such as the potential of the mean force, minimum free energy path, the diffusion constant, and the transition rate remain invariant under coordinate transformation due to the Riemannian treatment of the collective variable space. Specific algorithms within this framework are discussed such as the Riemannian umbrella sampling, the Riemannian string method, and a Riemannian-Bayesian estimator of free energy and diffusion constant, which can be used to estimate the transition rate along a minimum free energy path.

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