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.

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

A robust approach to estimating rates from time-correlation functions

John D. ChoderaPhillip J. ElmsWilliam C. SwopeJan-Hendrik PrinzSusan MarquseeCarlos BustamanteFrank NoéVijay 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.

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.

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.

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.

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

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

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

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

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.