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