Designing Free Energy Surfaces That Match Experimental Data with Metadynamics
| Autor: | Gregory A. Voth, James F. Dama, Andrew D. White |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Journal of Chemical Theory and Computation. 11:2451-2460 |
| ISSN: | 1549-9626 1549-9618 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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