title: Designing free energy surfaces that match experimental data with metadynamics.
abstract: Creating models that are consistent with experimental data is essential in molecular modeling. This is often done by iteratively tuning the molecular force field of a simulation to match experimental data. An alternative method is to bias a simulation, leading to a hybrid model composed of the original force field and biasing terms. We previously introduced such a method called experiment directed simulation (EDS). EDS minimally biases simulations to match average values. In this work, we introduce a new method called experiment directed metadynamics (EDM) that creates minimal biases for matching entire free energy surfaces such as radial distribution functions and phi/psi angle free energies. It is also possible with EDM to create a tunable mixture of the experimental data and free energy of the unbiased ensemble with explicit ratios. EDM can be proven to be convergent, and we also present proof, via a maximum entropy argument, that the final bias is minimal and unique. Examples of its use are given in the construction of ensembles that follow a desired free energy. The example systems studied include a Lennard-Jones fluid made to match a radial distribution function, an atomistic model augmented with bioinformatics data, and a three-component electrolyte solution where ab initio simulation data is used to improve a classical empirical model.
authors.affiliation: Department of Chemistry, James Franck Institute, Institute for Biophysical Dynamics, and Computation Institute, The University of Chicago , 5735 South Ellis Avenue, Chicago, Illinois 60637, United States.|Center for Nonlinear Studies, Theoretical Division, Los Alamos National Laboratory , Los Alamos, New Mexico 87545, United States.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: White
authors.affiliation: Department of Chemistry, James Franck Institute, Institute for Biophysical Dynamics, and Computation Institute, The University of Chicago , 5735 South Ellis Avenue, Chicago, Illinois 60637, United States.|Center for Nonlinear Studies, Theoretical Division, Los Alamos National Laboratory , Los Alamos, New Mexico 87545, United States.
authors.forename: James F
authors.initials: JF
authors.lastname: Dama
authors.affiliation: Department of Chemistry, James Franck Institute, Institute for Biophysical Dynamics, and Computation Institute, The University of Chicago , 5735 South Ellis Avenue, Chicago, Illinois 60637, United States.|Center for Nonlinear Studies, Theoretical Division, Los Alamos National Laboratory , Los Alamos, New Mexico 87545, United States.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth