Integrated variational approach to conformational dynamics: A robust strategy for identifying eigenfunctions of dynamical operators
The Journal of Physical Chemistry B, 2020•ACS Publications
One approach to analyzing the dynamics of a physical system is to search for long-lived
patterns in its motions. This approach has been particularly successful for molecular
dynamics data, where slowly decorrelating patterns can indicate large-scale conformational
changes. Detecting such patterns is the central objective of the variational approach to
conformational dynamics (VAC), as well as the related methods of time-lagged independent
component analysis and Markov state modeling. In VAC, the search for slowly decorrelating …
patterns in its motions. This approach has been particularly successful for molecular
dynamics data, where slowly decorrelating patterns can indicate large-scale conformational
changes. Detecting such patterns is the central objective of the variational approach to
conformational dynamics (VAC), as well as the related methods of time-lagged independent
component analysis and Markov state modeling. In VAC, the search for slowly decorrelating …
One approach to analyzing the dynamics of a physical system is to search for long-lived patterns in its motions. This approach has been particularly successful for molecular dynamics data, where slowly decorrelating patterns can indicate large-scale conformational changes. Detecting such patterns is the central objective of the variational approach to conformational dynamics (VAC), as well as the related methods of time-lagged independent component analysis and Markov state modeling. In VAC, the search for slowly decorrelating patterns is formalized as a variational problem solved by the eigenfunctions of the system’s transition operator. VAC computes solutions to this variational problem by optimizing a linear or nonlinear model of the eigenfunctions using time series data. Here, we build on VAC’s success by addressing two practical limitations. First, VAC can give poor eigenfunction estimates when the lag time parameter is chosen poorly. Second, VAC can overfit when using flexible parametrizations such as artificial neural networks with insufficient regularization. To address these issues, we propose an extension that we call integrated VAC (IVAC). IVAC integrates over multiple lag times before solving the variational problem, making its results more robust and reproducible than VAC’s.
ACS Publications
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