AGBNP   |  GaussVol   | BEDAM | ASyncRE IMPACT | UWHAM

AGBNP OpenMM Plugin

AGBNP (see AGBNP and AGBNP2 publications) is an analytic implicit hydration model primarily aimed at alchemical binding free energy calculations. The legacy CPU version of AGBNP is freely available as a portable library written in C. More recently, we have been focusing on a GPU implementation of AGBNP as part of the OpenMM library which is many times faster than the best CPU implementation. The AGBNP OpenMM Plugin freely available on github under the GPL license. The plugin currently implements on GPUs AGBNP version 1 (as well as the GaussVol model, see below). The GPU implementation of AGBNP2 is underway.  

GaussVol OpenMM Plugin

overlap tree
The GaussVol plugin implements in OpenMM the Gaussian model of Grants & Pickup for the fast calculation of the volume and surface area of macromolecules. The model is the basis of the AGBNP model above. The plugin enables molecular dynamics simulations on GPUs with an effective potential energy function proportional to the solute volume and/or the solute surface area as in, for instance, models of hydrophobic solvation. The GPU implementation is described in a publication in the Journal of Computational Chemistry. The original GaussVol plugin code is available on github. Development and support of GaussVol continue as part of the AGBNP OpenMM Plugin described above.

BEDAM Binding Free Energy Estimation

The BEDAM Binding Energy Distribution Analysis Method is an absolute binding free energy estimation and analysis methodology based on a statistical mechanics theory of molecular association and efficient computational strategies built upon parallel Hamiltonian replica exchange, implicit solvation and multi-state statistical inference. It has been implemented into a python workflow that works within the Schrödinger environment with the IMPACT MD engine.

Free download of BEDAM workflow

The workflow It takes as input .mae files of receptor and ligand plus a definition of the binding site region. Analysis of the results produce, among other things, the estimated values of the binding free energy. See the documentation and example provided.

Thanks to a generous grant from the NSF, BEDAM is being implemented also in the popular OpenMM package.

Asynchronous Replica Exchange Framework

Asynchronous replica exchange (or ASyncRE for short) is an implementation of the popular parallel replica exchange conformational sampling algorithm. Unlike traditional synchronous implementations, ASyncRE can scale to many hundreds of replicas over heterogeneous grids of unreliable compute nodes for long running times.

ASyncRE software

IMPACT Molecular Simulation Program

IMPACT is a molecular mechanics and molecular dynamics engine developed starting in the 1980's in Ron Levy's group at Rutgers University. Starting in 2000 development continued jointly at Rutgers and at Schrödinger Inc. Many of Schrödinger's products for structure-based drug discovery (Glide, Liaison, QSite, SiteMap, ProPrep, PrimeX) are based on the IMPACT molecular mechanics engine. I have contributed to some of these products as well as to the integration of IMPACT with the Maestro GUI. Recent academic development has been mainly centered on implicit solvent modeling (AGBNP, above), on replica exchange advanced conformational sampling (see for example ASyncRE, below), and protein-ligand binding free energy modeling (BEDAM).

Unbinned-WHAM R Package

UWHAM is a R package for multi-state free energy estimation and thermodynamic reweighting I developed jointly with Zhiqiang Tan at the Department of Statistics at Rutgers University. It provides to R users functionality similar to the MBAR python package. MBAR and UWHAM return identical point estimates of free energies and expectations using different numerical routes. See the UWHAM publication.

To install UWHAM enter:

> install.packages("UWHAM")

within a R session. Documentation and examples are available within R by entering

> library("UWHAM")
> help(uwham)

or in pdf format from

Variance estimation is based on the Fisher or Sandwich formulas, or, for correlated data, by block bootstrap. Processes corresponding to multiple independent simulations, serial tempering or serial Hamiltonian hopping simulations, and parallel replica exchange simulations of both the synchronous and asynchronous varieties are supported.

The UWHAM package is particularly robust in terms of scalability; we have been able to process within minutes large 2D replica exchange datasets with ~300,000 snapshots from ~200 thermodynamic states. Feedback, comments, and bug reports