Kinetic Distance and Kinetic Maps from Molecular Dynamics Simulation
Frank Noé,Cecilia Clementi +1 more
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TLDR
A kinetic distance metric for irreducible Markov processes that quantifies how slowly molecular conformations interconvert is defined and the total kinetic variance (TKV) is an excellent indicator of model quality and can be used to rank different input feature sets.Abstract:
Characterizing macromolecular kinetics from molecular dynamics (MD) simulations requires a distance metric that can distinguish slowly interconverting states. Here, we build upon diffusion map theory and define a kinetic distance metric for irreducible Markov processes that quantifies how slowly molecular conformations interconvert. The kinetic distance can be computed given a model that approximates the eigenvalues and eigenvectors (reaction coordinates) of the MD Markov operator. Here, we employ the time-lagged independent component analysis (TICA). The TICA components can be scaled to provide a kinetic map in which the Euclidean distance corresponds to the kinetic distance. As a result, the question of how many TICA dimensions should be kept in a dimensionality reduction approach becomes obsolete, and one parameter less needs to be specified in the kinetic model construction. We demonstrate the approach using TICA and Markov state model (MSM) analyses for illustrative models, protein conformation dynamics in bovine pancreatic trypsin inhibitor and protein-inhibitor association in trypsin and benzamidine. We find that the total kinetic variance (TKV) is an excellent indicator of model quality and can be used to rank different input feature sets.read more
Citations
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Journal ArticleDOI
PyEMMA 2: A Software Package for Estimation, Validation, and Analysis of Markov Models.
Martin K. Scherer,Benjamin Trendelkamp-Schroer,Fabian Paul,Guillermo Pérez-Hernández,Moritz Hoffmann,Nuria Plattner,Christoph Wehmeyer,Jan-Hendrik Prinz,Frank Noé +8 more
TL;DR: The open-source Python package PyEMMA is presented, derived a systematic and accurate way to coarse-grain MSMs to few states and to illustrate the structures of the metastable states of the system.
Journal ArticleDOI
Markov State Models: From an Art to a Science
Brooke E. Husic,Vijay S. Pande +1 more
TL;DR: An overview of the MSM field to date is presented, presented for a general audience as a timeline of key developments in the field, and the current frontiers of methods development are highlighted, as well as exciting applications in experimental design and drug discovery.
Journal ArticleDOI
VAMPnets for deep learning of molecular kinetics.
TL;DR: A deep learning framework that automates construction of Markov state models from MD simulation data is introduced that performs equally or better than state-of-the-art Markov modeling methods and provides easily interpretable few-state kinetic models.
Journal ArticleDOI
Time-lagged autoencoders: Deep learning of slow collective variables for molecular kinetics.
Christoph Wehmeyer,Frank Noé +1 more
TL;DR: It is shown that the time-lagged autoencoder reliably finds low-dimensional embeddings for high-dimensional feature spaces which capture the slow dynamics of the underlying stochastic processes-beyond the capabilities of linear dimension reduction techniques.
Journal ArticleDOI
Data-driven model reduction and transfer operator approximation
Stefan Klus,Feliks Nüske,Péter Koltai,Hao Wu,Ioannis G. Kevrekidis,Ioannis G. Kevrekidis,Christof Schütte,Christof Schütte,Frank Noé +8 more
TL;DR: In this article, the authors present different data-driven dimension reduction techniques for dynamical systems that are based on transfer operator theory as well as methods to approximate transfer operators and their eigenvalues, eigenfunctions, and eigenmodes.
References
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TL;DR: Simulation of the folding of a WW domain showed a well-defined folding pathway and simulation of the dynamics of bovine pancreatic trypsin inhibitor showed interconversion between distinct conformational states.