UFEDMM extends OpenMM's Python API so that the user can easily run efficient simulations in extended phase spaces, perform enhanced sampling of systems with barriers and rare events, and compute accurate free-energy surfaces for collective variables or reaction coordinates.
The concept of extended phase space is a powerful tool in Molecular Dynamics. It consists in treating arbitrary variables as coordinates of fictitious particles, assigning masses to these particles, and solving equations of motion which encode their interactions with the system molecules. Differently from collective variables, which are functions of atomic coordinates, these extra dynamical variables are independent ones. Together with their conjugate momenta, they add new dimensions to the system's phase space.
Free energy is an important thermodynamic property that quantifies the relative likelihood of different states of a system. UFEDMM uses extended phase-space dynamics to facilitate the calculation of free energy as a function of extra dynamical variables. Under certain assumptions, this is a suitable approximation for the free energy as a function of collective variables, also known as potential of mean force (PMF).
UFEDMM combines two methods to efficiently overcome free-energy barriers. The TAMD/d-AFED method heats the extended variables to a higher temperature than the one specified for the molecules. The Metadynamics method floods free-energy basins with potential energy so that barriers are eventually smoothed out. This is the Unified Free Energy Dynamics (UFED) method: heating and flooding, all at once.
Interaction between a fictitious particle and the actual molecules is enacted by adding, to the total potential energy of the system, a new term that depends both on the corresponding dynamical variable and at least one collective variable. With OpenMM's CustomCVForce class, adding such a term is as simple as writing down a mathematical expression. All the low-level coding and compilation takes place automatically in the background.
UFEDMM build on the customization capability of OpenMM to enable efficient UFED simulations in GPU's and other parallel computation platforms. It is efficient because it makes OpenMM treat extra dynamical variables like normal atomic coordinates, thus avoiding the computational overhead of dealing with Context parameters.
TAMD/d-AFED is optionally enabled by assigning distinct temperatures to the molecules and to the extra dynamical variables. For this, UFEDMM provides special CustomIntegrator subclasses, given that the intrinsic OpenMM integrators cannot handle multiple temperatures. Extended-space Metadynamics is enabled by explicitly defining the height and widths of Gaussian hills to be deposited over time, as well as the deposition period.
For the post-processing of UFED simulations, a free energy analysis tool is provided, which is based on mean-force estimation and radial basis set reconstruction of free energy (hyper)surfaces.
In OpenMM, a collective variable (CV) involved in a CustomCVForce are
nothing but objects of some Force (or, particularly, CustomForce)
subclass. The user is free to define any CV for a UFED simulation. For
convenience, through, UFEDMM provides a module with several predefined
CV's, such as:
- Square radius of gyration of a group of atoms
- Number of contacts between two groups of atoms
- Different flavors of alpha-helix content measures, based on angles, dihedrals, and hydrogen bonds
The ufedmm.cvlib module can be viewed as a standalone package of
general applicability, not restricted to ufedmm simulations.
https://ufedmm.readthedocs.io/en/latest
This is an open-source (MIT licensed) project. Contribution is welcome.
Project structure based on the Computational Molecular Science Python Cookiecutter version 1.0.