Molecular dynamics simulations necessarily use a finite timestep, which introduces error or bias in the sampled configuration space density that grows rapidly with increasing timestep. For the first time, we show how to compute a natural measure of this error---the KL divergence---in both phase and configuration space for a widely used family of Langevin integrators, and show that VRORV is generally superior for simulation of molecular systems.
We review alchemical methods for computing solvation free energies and present an update (version 0.5) to the FreeSolv database of experimental and calculated hydration free energies of neutral compounds.
We demonstrate a new tool that enables---for the first time---massively parallel molecular simulation studies of biomolecular dynamics at the superfamily scale, illustrating its application to protein tyrosine kinases, an important class of drug targets in cancer.
We present a simple scheme for automatically selecting how much initial simulation data to discard to equilibration or burn-in based on maximizing the number of statistically uncorrelated samples in the dataset.
Keywords: molecular simulation; molecular dynamics; burn-in; equilibration; production; analysis
Kyle A. Beauchamp, Julie M. Behr, Ariën S. Rustenburg, Christopher I. Bayly, Kenneth Kroenlein, and John D. Chodera.
J. Phys. Chem. B 119:12912, 2015. [DOI] [PDF] // code: [GitHub] // preprint: [arXiv]
Progress in forcefield validation and parameterization has been hindered by the availability of high-quality machine-readable physical property data for small organic molecules. We show how the NIST ThermoML dataset provides a solution to this problem, and demonstrate its utility in benchmarking the GAFF/AM1-BCC small molecule forcefield on neat liquid densities and static dielectric constants to uncover problems in the representation of low-dielectric environments.
We present a new mathematical framework for unifying various two-state rate theories presented in the physical chemistry literature over many decades, and provide a quantitative way to measure reaction coordinate quality.
We show how bound ligand poses can be identified even when the location of the binding sites are unknown using the machinery of alchemical modern free energy calculations on graphics processors.
A new inexpensive polarizable model of liquid water for next-generation forcefields is derived using an automated parameterization engine.
The finite-timestep errors in molecular dynamics simulations can be interpreted as a form of nonequilibrium work. We show how this leads to straightforward schemes for correcting for these errors or assessing their impact.
Keywords: velocity verlet with Velocity randomization; VVVR; nonequilibrium free energy; integrator error; nonequilibrium integration
Peter Eastman, Mark S. Friedrichs, John D. Chodera, Randy J. Radmer, Chris M. Bruns, Joy P. Ku, Kyle A. Beauchamp, T. J. Lane, Lee-Ping Wang, Diwakar Shukla, Tony Tye, Mike Houston, Timo Stich, Christoph Klein, Michael R. Shirts, and Vijay S. Pande.
J. Chem. Theor. Comput. 9:461, 2013. [DOI] [PDF]
We describe the latest version of an open-source, GPU-accelerated library and toolkit for molecular simulation.
We present a significant generalization of Monte Carlo methods that provide an enormously useful tool for enhancing the efficiency of molecular simulations and enabling molecular design.
Keywords: NCMC; Monte Carlo; Metropolis-Hastings; acceptance rates; molecular dynamics
We describe how reweighing techniques can provide optimal estimates of temperature-dependent dynamical properties from simulations conducted at multiple temperatures.
A review of current best practices for the generation and validation of Markov state models for describing the stochastic dynamics of biomolecular systems.
Molecular simulations of the PCNA clamp responsible for DNA polymerase processivity show a surprisingly small energetic penalty for the deformation required for clamp loading.
Jay W. Ponder, Chuanjie Wu, Pengyu Ren, Vijay S. Pande, John D. Chodera, David L. Mobley, Michael J. Schnieders, Imran Haque, David S. Lambrecht, Robert A. DiStasio Jr., Martin Head-Gordon, Gary N. I. Clark, Margaret E. Johnson, and Teresa Head-Gordon.
J. Phys. Chem. B 114:2549, 2010. [DOI] [PDF]
A report on the status of the AMOEBA polarizable force field and its ability to reproduce a diverse set of physical chemical phenomenon to high accuracy.
A Bayesian scheme for comparing state space decompositions for Markov state models of biomolecular dynamics that incorporates the fact that physical systems must obey detailed balance. This paper utilizes recent results from Markov chain theory on edge-reinforced random walks.