Sodium channels initiate signaling in neurons and other cells which go on to become sensations of pleasure and pain, as well as thoughts and feelings. In a collaboration with the duBois lab and with the help of Folding@Home, we are launching a large scale molecular dynamics study of the voltage gated sodium channel.

We’re studying the dynamics of transitions between the open and closed states mediated by the voltage sensing domains. Our experimental collaborators will probe sodium channel function through the use of natural toxins secreted by frogs in the Amazon rain forest. By combining theory and experiment, we can propose and test derivatives of these toxins which have positive therapeutic effects.

Our lab develops and applies novel statistical techniques to understand and interpret the huge volume of data returned from a molecular dynamics study. Particularly, we use Markov State Models (MSMs) which model conformational dynamics as a series of memoryless jumps between microstates.

I’ve introduced a new method for including solvent degrees of freedom in MSM analysis. Check out the paper introducing the method and the code. We’re working on applying it to new and exciting systems.

MSMs offer a convenient framework for analyzing the results of simulations, but they can also be used to direct simulation. In an adaptive sampling scheme, uncertainty in particular MSM state transition probabilities are used to seed new simulations to speed convergence of the model.

##### Conserve Water: A Method for the Analysis of Solvent in Molecular Dynamics

Matthew P. Harrigan; Diwakar Shukla; Vijay S. Pande

February 12, 2015

J. Chem. Theory Comput., 2015, 11 (3), pp 1094--1101. doi:10.1021/ct5010017 [pdf]##### MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories

Robert T. McGibbon; Kyle A. Beauchamp; Matthew P. Harrigan; Christoph Klein; Jason M. Swails; Carlos X. Hernández; Christian R. Schwantes; Lee-Ping Wang; Thomas J. Lane; Vijay S. Pande

October 20, 2015

Biophys. J., 109, 8, pp 1528--1532. doi:10.1016/j.bpj.2015.08.015 [bioRxiv] [pdf]##### User-friendly software for analyzing MD simulations

December 01, 2015

Nature Methods 12, 1116. doi:10.1038/nmeth.3669##### Osprey: Hyperparameter Optimization for Machine Learning

Robert T. McGibbon; Carlos X. Hernández; Matthew P. Harrigan; Steven Kearnes; Mohammad M. Sultan; Stanislaw Jastrzebski; Brooke E. Husic; Vijay S. Pande

September 07, 2016

JOSS, 1, 5. doi:10.21105/joss.00034##### MSMBuilder: Statistical Models for Biomolecular Dynamics

Matthew P. Harrigan; Mohammad M. Sultan; Carlos Xavier Hernandez; Brooke E. Husic; Peter Eastman; Christian R. Schwantes; Kyle A. Beauchamp; Robert T. McGibbon; Vijay S. Pande

January 10, 2017

Biophys. J., 112, 10--15. doi:10.1016/j.bpj.2016.10.042 [bioRxiv]##### OpenMM 7: Rapid Development of High Performance Algorithms for Molecular Dynamics

Peter Eastman; Jason Swails; John D. Chodera; Robert T. McGibbon; Yutong Zhao; Kyle A. Beauchamp; Lee-Ping Wang; Andrew C. Simmonett; Matthew P. Harrigan; Bernard R. Brooks; Vijay S. Pande

December 06, 2016

bioRxiv. doi:10.1101/091801##### Markov modeling reveals novel intracellular modulation of the human TREK-2 selectivity filter

Matthew P. Harrigan; Keri A. McKiernan; Veerabahu Shanmugasundaram; Rajiah Aldrin Denny; Vijay S. Pande

December 07, 2016

bioRxiv. doi:10.1101/092155