Systematic improvement of a classical molecular model of water

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.

Entropy-enthalpy compensation: Role and ramifications for rational ligand design

John D. Chodera and David L. Mobley.
Annu. Rev. Biophys. 42:121, 2013. [DOI] [PDF]

Entropy-enthalpy compensation is likely a universal phenomena, but not as severe as widely thought, and likely not of enormous concern for drug discovery and ligand design.

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

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

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

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.

On the use of experimental observations to bias simulated ensembles

Jed W. Pitera and John D. Chodera.
J. Chem. Theor. Comput. 8:3445, 2012. [DOI] [PDF]

We show how the concept of maximum entropy can be used to recover unbiased conformational distributions from experimental data, and how this concept relates to the popular `ensemble refinement' schemes for NMR data analysis.

The molten globule state is unusually deformable under mechanical force

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

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

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

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

Splitting probabilities as a test of reaction coordinate choice in single-molecule experiments

John D. Chodera and Vijay S. Pande.
Phys. Rev. Lett. 107:098102, 2011. [DOI] [PDF]

We demonstrate a simple test for identifying poor reaction coordinates in single-molecule experiments.

A robust approach to estimating rates from time-correlation functions

John D. Chodera, Phillip J. Elms, William C. Swope, Jan-Hendrik Prinz, Susan Marqusee, Carlos Bustamante, Frank Noé, Vijay S. Pande
Preprint ahead of submission: [arXiv] [PDF] [SI]

The estimation of rates from experimental single-molecule data is fraught with peril. We describe some of the failures of existing methods and suggest a robust way to estimate rates from time-correlation functions.

The Social Network (of protein conformations)

John D. Chodera and Vijay S. Pande.
Proc. Natl. Acad. Sci. USA 108:12969, 2011. [DOI] [PDF]

Commentary: A new methodology for mapping protein conformational spaces is reminiscent of how we use two-dimensional maps to navigate a three-dimensional world.

Bayesian hidden Markov model analysis of single-molecule force spectroscopy: Characterizing kinetics under measurement uncertainty

John D. Chodera, Phillip Elms, Frank Noé, Bettina Keller, Christian M. Kaiser, Aaron Ewall-Wice, Susan Marqusee, Carlos Bustamante, and Nina Singhal Hinrichs.
preprint: [arXiv]

We describe the general theory and implementation for a Bayesian extension of hidden Markov models applicable to the characterization of how measurement uncertainty and finite statistics can impact the confidence in rate constants and conformational state properties.

Systematic errors in isothermal titration calorimetry: Concentrations and baselines

Joel T. Tellinghuisen and John D. Chodera.
Anal. Biochem. 414:297, 2011. [DOI] [PDF]

A word of caution about large errors in isothermal titration calorimetry measurements arising from ligand concentration errors.

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

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.

Optimal use of data in parallel tempering simulations for the construction of discrete-state Markov models of biomolecular dynamics

Jan-Hendrik Prinz, John D. Chodera, Vijay S. Pande, Jeremy C. Smith, and Frank Noé.
J. Chem. Phys. 134:244108, 2011. [DOI] [PDF]

Markov models of molecular kinetics: Generation and validation

Jan-Hendrik Prinz, Hao Wu, Marco Sarich, Bettina Keller, Martin Fischbach, Martin Held, John D. Chodera, Christof Schüttle, and Frank Noé.
J. Chem. Phys. 134:174105, 2011. [DOI] [PDF]

A review of current best practices for the generation and validation of Markov state models for describing the stochastic dynamics of biomolecular systems.

Free energy methods in drug discovery and design: Progress and challenges

John D. Chodera, David L. Mobley, Michael R. Shirts, Richard W. Dixon, Kim M. Branson, and Vijay S. Pande.
Curr. Opin. Struct. Biol. 21:150, 2011. [DOI] [PDF]

A review of the opportunities and challenges for alchemical free energy calculations in drug discovery and design.

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

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.