Identifying ligand binding sites and poses using GPU-accelerated Hamiltonian replica exchange molecular dynamics

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Kai Wang K, John D. Chodera, Yanzhi Yang, and Michael R. Shirts. 
J. Comput. Aid. Mol. Des. 27:989, 2013. [DOI] [PDF]

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. 

Systematic improvement of a classical molecular model of water

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Lee-Ping Wang, Teresa L. Head-Gordon, Jay W. Ponder, Pengyu Ren, John D. Chodera, Peter K. Eastman, Todd J. Martinez, and Vijay S. Pande.
J. Phys. Chem. B 117:9956, 2013. [DOI] [PDF]

A new inexpensive polarizable model of liquid water for next-generation forcefields is derived using an automated parameterization engine.

 

Using nonequilibrium fluctuation theorems to understand and correct errors in equilibrium and nonequilibrium discrete Langevin dynamics simulations

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David A. Sivak, John D. Chodera, and Gavin E. Crooks.
Phys. Rev. X 3:011007, 2013. [DOI] [PDF]

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

OpenMM 4: A reusable, extensible, hardware independent library for high performance molecular simulation

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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.

The limitations of constant-force-feedback experiments

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Phillip J. Elms, John D. Chodera, Carlos J. Bustamante, and Susan Marqusee.
Biophys. J. 103:1490, 2012. [DOI] [PDF]

Popular constant-force-feedback single-molecule experiments can cause severe artifacts in single-molecule force spectroscopy data.  We demonstrate a simple alternative that eliminates these artifacts.

The molten globule state is unusually deformable under mechanical force

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Philip J. Elms, John D. Chodera, Carlos Bustamante, and Susan Marqusee.
Proc. Natl. Acad. Sci. USA 109:3796, 2012. [DOI] [PDF]

We measure the physical properties of the molten globule state of apo-myoglobin, and show that it is unusually deformable compared to typical protein native states.

Replica exchange and expanded ensemble simulations as Gibbs sampling: Simple improvements for enhanced mixing

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John D. Chodera and Michael R. Shirts.
J. Chem. Phys. 135:194110, 2011. [DOI] [PDF] 

We show how a simple change to the way exchanges are handled in the popular replica-exchange simulation methodology can enormously increase efficiency at no increase in computational cost.

The ribosome modulates nascent protein folding

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Christian M. Kaiser, Daniel H. Goldman, John D. Chodera, Ignacio Tinoco Jr., and Carlos Bustamante.
Science 334:1723, 2011. [DOI] [PDF]

Using single-molecule force spectroscopy, we show how the ribosome itself modulates the folding dynamics of nascent protein chains emerging from the exit tunnel.

Nonequilibrium candidate Monte Carlo is an efficient tool for equilibrium simulation

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Jerome P. Nilmeier, Gavin E. Crooks, David D. L. Minh, and John D. Chodera. 
Proc. Natl. Acad. Sci. USA 108:E1009, 2011. [DOI] [PDF]

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

Dynamical reweighting: Improved estimates for dynamical properties from simulations at multiple temperatures

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John D. Chodera, William C. Swope, Frank Noé, Jan-Hendrik Prinz, Michael R. Shirts, and Vijay S. Pande.
J. Chem. Phys. 134:244107, 2011. [DOI] [PDF] 

We describe how reweighing techniques can provide optimal estimates of temperature-dependent dynamical properties from simulations conducted at multiple temperatures.

Dynamical fingerprints: A theoretical framework for understanding biomolecular processes by combination of simulation and kinetic experiments

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Frank Noé, Sören Doose, Isabella Daidone, Marc Löllmann, Markus Sauer, John D. Chodera, and Jeremy C. Smith.
Proc. Natl. Acad. Sci. USA 108:4822, 2011. [DOI] [PDF]

We present a new framework for comparing essential features of the dynamics between experiment and simulation to identify the kinetics processes contributing to individual relaxation timescales in perturbation-response or correlation spectroscopy experiments.

Estimating equilibrium ensemble averages using multiple time slices from driven nonequilibrium processes

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Estimating equilibrium ensemble averages using multiple time slices from driven nonequilibrium processes: Theory and application to free energies, moments, and thermodynamic length in single-molecule pulling experiments
David D. L. Minh and John D. Chodera
J. Chem. Phys. 134:024111, 2011. [DOI] [PDF]

We derive a new estimator for estimating equilibrium expectations from nonequilibrium experiments, and show how it can be used to estimate a variety of useful quantities in simulated single-molecule force spectroscopy experiments.

Probability distributions of molecular observables computed from Markov models. II. Uncertainties in observables and their time-evolution

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John D. Chodera and Frank Noé.
J. Chem. Phys. 133:105102, 2010. [DOI] [PDF]

A simple Bayesian approach for the modeling of statistical uncertainties in kinetic and equilibrium quantities computed from Markov state models of biomolecular dynamics.

The mechanical properties of PCNA: Implications for the loading and function of a DNA sliding clamp

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Joshua L. Adelman, John D. Chodera, I. W. Kuo, Thomas F. Miller III, and Daniel Barsky.
Biophys. J. 98:3062, 2010. Featured on issue cover. [DOI] [PDF]

Molecular simulations of the PCNA clamp responsible for DNA polymerase processivity show a surprisingly small energetic penalty for the deformation required for clamp loading.

Current status of the AMOEBA polarizable force field

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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.

Optimal estimators and asymptotic variances for nonequilibrium path-ensemble averages

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David D. D. L. Minh and John D. Chodera.
J. Chem. Phys. 131:134110, 2009. [DOI] [PDF]

We derive an optimal estimator and corresponding statistical uncertainties for inferring expectations of bidirectional nonequilibrium processes.  These estimators have widespread applicability in single-molecule biophysical force-spectroscopy experiments and nonequilibrium molecular simulations.

Statistically optimal analysis of samples from multiple equilibrium states

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Michael R. Shirts and John D. Chodera.  
J. Chem. Phys. 129:124105, 2008. [DOI] [PDF]

We present a highly general, statistically optimal approach for producing estimates of free energies and equilibrium expectations from multiple simulations that provably extracts all useful information from the data.

Keywords: Multistate Bennett acceptance ratio; MBAR; Bennett acceptance ratio; BAR; molecular dynamics; Monte Carlo; replica exchange