Bayesian comparison of Markov models of molecular dynamics with detailed balance constraint

Sergio Bacallado, John D. Chodera, and Vijay S. Pande.
J. Chem. Phys. 131:045106, 2009. [DOI] [PDF] 

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.

Statistically optimal analysis of samples from multiple equilibrium states

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

Technical Report: Self-consistent definition and computation of the electrostatic field for the Amber and related forcefields with particle-mesh Ewald

John D. Chodera. Technical report.  [PDF]

This technical report provides information on the computation of the electric field and its gradient for the Amber forcefield in particle-mesh Ewald (PME) in AMBER 10. 

Predicting small-molecule solvation free energies: A blind challenge test for computational chemistry

Anthony Nicholls, David L. Mobley, J. Peter Guthrie, John D. Chodera, and Vijay S. Pande.
J. Med. Chem. 51:769, 2008. [DOI] [PDF]

A blind evaluation of the accuracy of alchemical free energy methods for computing gas-to-water transfer free energies (solvation free energies) of small molecules demonstrates that modern forcefields are likely sufficiently accurate to be useful in drug design.

Treating entropy and conformational changes in implicit solvent simulations of small molecules

David L. Mobley, John D. Chodera, and Ken A. Dill
J. Phys. Chem. B 112:938, 2008. [DOI] [PDF]

A quantitative examination of how much conformational entropy contributes to hydration free energies of small molecules, with implications for ligand binding.

Accurate and efficient corrections for missing dispersion interactions in molecular simulations

Michael R. Shirts, David L. Mobley, John D. Chodera, and Vijay S. Pande.  
J. Phys. Chem. B 111:13052, 2007. [DOI] [PDF]

We identify a major source of systematic error in absolute alchemical free energy calculations of ligand binding and show how a simple procedure can inexpensively and accurately eliminate it.

Alchemical free energy calculations: Ready for prime time?

Michael R. Shirts, David L. Mobley, and John D. Chodera.
Annu. Rep. Comput. Chem. 3:41, 2007. [DOI] [PDF]

A review of current alchemical free energy methodologies assessing whether they are ready for practical use in drug discovery and ligand design.

Predicting absolute ligand binding free energies to a simple model site.

David L. Mobley, Alan P. Graves, John D. Chodera, Andrea C. McReynolds, Brian K. Shoichet, and Ken A. Dill.
J. Mol. Biol. 371:1118, 2007. [DOI] [PDF]

We show how alchemical free energy calculations are capable of accurate blind prediction of small-molecule binding affinities to a simple model protein binding site.

The protein folding problem: When will it be solved?

Ken A. Dill, S. Banu Ozkan, Thomas R. Weikl, John D. Chodera, and Vincent A. Voelz.
Curr. Opin. Struct. Biol. 17:342, 2007. [DOI] [PDF]

A review of the current state of the protein folding problem.

Confine-and-release method: Obtaining correct binding free energies in the presence of protein conformational change

David L. Mobley, John D. Chodera, and Ken A. Dill.
J. Chem. Theor. Comput. 3:1231, 2007. [DOI] [PDF]

We present a general scheme for obtaining correct ligand binding affinities when protein conformational change is implicated in ligand binding.

Protein Folding by Zipping and Assembly

S. Banu Ozkan, G. Albert Wu, John D. Chodera, and Ken A. Dill.
Proc. Natl. Acad. Sci. USA 104:11987, 2007. [DOI] [PDF]

A review of the utility of the proposed zipping and assembly mechanism for the concomitant formation of secondary and tertiary structure in protein folding for predicting folding pathways and native structures.

Automatic discovery of metastable states for the construction of Markov models of macromolecular conformational dynamics

John D. Chodera*, Nina Singhal*, William C. Swope, Jed W. Pitera, Vijay S. Pande, and Ken A. Dill.
J. Chem. Phys. 126:155101, 2007. [DOI] [PDF]

Proposing one of the first automated algorithms for discovering kinetically metastable states of biomolecules from molecular simulations, this paper shows how many biomolecules can possess numerous distinct long-lived conformational states even though the the equilibrium populations of these states may too small for standard structural biology techniques to detect.

Comparison of charge models for fixed-charge force fields: Small-molecule hydration free energies in explicit solvent

David L. Mobley, Élise Dumont, John D. Chodera, Christopher I. Bayly, Matthew D. Cooper, and Ken A. Dill.
J. Phys. Chem. B 111:2242, 2007. [DOI] [PDF]

We compare a number of popular methods for deriving charge models for small molecules, deriving lessons about best practices for accurate simulations.

Long-time protein folding dynamics from short-time molecular dynamics simulations

John D. Chodera, William C. Swope, Jed W. Pitera, and Ken A. Dill.
Multiscale Model. Simul. 5:1214, 2006. [DOI] [PDF]

We show how the long-time dynamics of biomolecular systems can be recapitulated from statistics collected from short molecular simulations sampling transitions between kinetically metastable states.

Use of the weighted histogram analysis method for the analysis of simulated and parallel tempering simulations

John D. Chodera, William C. Swope, Jed W. Pitera, Chaok Seok, and Ken A. Dill.
J. Chem. Theor. Comput. 3(1):26–41, 2007 [DOI] [PDF]

The weighted histogram analysis method (WHAM), a mainstay of molecular dynamics simulation analysis, is thoroughly explained and modernized for the analysis of simulated and parallel tempering simulation data. 

On the use of orientational restraints and symmetry corrections in alchemical free energy calculations

David L. Mobley, John D. Chodera, and Ken A. Dill.
J. Chem. Phys. 125:084902, 2006. [DOI] [PDF]

We illustrate how orientational restraints can be used to greatly reduce the computational effort in alchemical calculations of ligand binding free energies, and clarify how symmetry corrections are necessary when molecules contain symmetric or pseudosymmetric substituents.

MOPED: Method for optimizing physical energy parameters using decoys

Chaok Seok, J. B. Rosen, John D. Chodera, and Ken A. Dill. 
J. Comput. Chem., 24(1):89-97 (2003) [DOI] [PDF]

We show how the long-time dynamics of biomolecular systems can be recapitulated from statistics collected from short molecular simulations sampling transitions between kinetically metastable states. 

An alternative explanation for the catalytic proficiency of orotidine 5'-phosphate decarboxylase

Tai-Sung Lee*, Lillian T. Chong*, John D. Chodera, and Peter A. Kollman. 
* These authors contributed equally to the work. 
J. Am. Chem. Soc., 123 (51):12837-12848 (2001) [DOI] [PDF]

A combined QM and MD analysis of potential plausible mechanisms to explain the enormous catalytic acceleration of one of the most proficient enzymes known.