BRIDGE

BRIDGE provides an open, reproducible environment for conducting biomolecular simulations and computing absolute and relative binding free energies to support computational studies of biomolecular interactions.

Key Features:

• Galaxy integration: Built on the Galaxy bioinformatics framework to orchestrate and share computational workflows.
• Hosted computational chemistry tools: Includes tools for molecular simulations and free-energy calculations.
• Docker containerization: Utilizes Docker containers for machine- and operating-system-independent deployment of workflows.
• Standardized workflows and protocols: Provides versioned, shareable protocols and workflows to improve reproducibility of computational methods.
• Free energy calculations: Supports absolute binding free energies (ABFEs) and relative binding free energies (RBFEs) using Free Energy Perturbation (FEP) methodologies and software such as GROMACS and YANK.
• Distributed computation: Supports large-scale computations across geographically dispersed servers, exemplified by cyclin-dependent kinase 2 (CDK2) FEP calculations performed across servers in Africa and Europe.
• Open protocol and result sharing: Enables public sharing of simulation protocols and results to facilitate external review and verification.

Scientific Applications:

• ST3Gal-I inhibitor evaluation: Applied RBFE and ABFE methods to compute binding free energies for potential inhibitors of β-galactoside α-2,3-sialyltransferase I (ST3Gal-I), a breast cancer drug target.
• CDK2 free-energy studies: Used for FEP calculations on cyclin-dependent kinase 2 (CDK2) in distributed compute settings to support collaborative computational studies.

Methodology:

Integration with the Galaxy framework; deployment via Docker containers; standardized, shareable workflows; free-energy methods including ABFE and RBFE implemented with Free Energy Perturbation (FEP) and executed with software such as GROMACS and YANK; distributed execution across multiple servers.