BRIDGE: An Open Platform for Reproducible Protein-Ligand Simulations and Free Energy of Binding Calculations.

Abstract

Protein-ligand binding prediction is central to the drug-discovery process. This often follows an analysis of genomics data for protein targets and then protei n structure discovery. However, the complexity of performing reproducible protein conformational analysis and ligand binding calculations, using vetted methods and protocols can be a challenge. Here we show how Biomolecular Reaction and Interaction Dynamics Global Environment (BRIDGE), an open-source web-based compute and analytics platform for computational chemistry developed based on the Galaxy bioinformatics platform, makes protocol sharing seamless following genomics and proteomics. BRIDGE makes available tools and workflows to carry out protein molecular dynamics simulations and accurate free energy computations of protein-ligand binding. We illustrate the dynamics and simulation protocols for predicting protein-ligand binding affinities in silico on the T4 lysozyme system. This protocol is suitable for both novice and experienced practitioners. We show that with BRIDGE, protocols can be shared with collaborators or made publicly available, thus making simulation results and computations independently verifiable and reproducible.