Identifying and Overcoming the Sampling Challenges in Relative Binding Free Energy Calculations of a Model Protein:Protein Complex

Zhang I, Rufa DA, Pulido I, Henry MM, Rosen LE, Hauser K, Singh S, Chodera JD
Journal of Chemical Theory and Computation 19:4863, 2023

We assess what is required for alchemical free energy calculations to be able to make high-quality predictions of the impact of interfacial mutations on protein-protein binding.

Improving force field accuracy by training against condensed-phase mixture properties

Boothroyd S, Madin OC, Mobley DL, Wang L-P, Chodera JD, and Shirts MR
Journal of Chemical Theory and Computation 18:3577, 2022 [DOI] [GitHub]

We use a new automated framework for physical property evaluation and fitting to show how molecular mechanics force fields can be systematically improved by fitting to condensed phase properties.

What Markov State Models can and cannot do: Correlation versus path-based observables in protein-folding models

Ernesto Suárez, Rafal P Wiewiora, Chris Wehmeyer, Frank Noé, John D Chodera, Daniel M Zuckerman
Journal of Chemical Theory and Computation 17:3119, 2021
[DOI] [PDF] [bioRxiv] [GitHub]

Markov state models are now well-established for describing the long-time conformational dynamics of proteins. Here, we take a critical look of what properties can reliably be extracted from these coarse-grained models.