RestraintMaker

RestraintMaker optimizes selection of distance restraints between molecular pairs to improve accuracy and sampling efficiency in relative binding free energy (RBFE) and other free-energy calculations.

Key Features:

• Graph-Based Approach: Employs a graph-based methodology using geometric measures to identify locally optimal distance restraints.
• Greedy Algorithm Implementation: Implements a greedy algorithm to systematically select restraints, reduce inter-molecular drift, and enhance sampling efficiency.
• Dual-Topology Compatibility: Designed for dual-topology RBFE workflows where molecules are simulated separately to facilitate high-throughput calculations.
• Multi-State Methods Support: Supports multi-state free-energy methods including enveloping distribution sampling (EDS) and multi-site dynamics.
• Output Formats: Exports selected distance restraints in GROMOS and GROMACS file formats and a human-readable JSON format.
• System Representation Categorization: Automates systematic categorization of system representations to address ambiguities in restraint definitions reported in the literature.

Scientific Applications:

• Relative Binding Free Energy Calculations: Improves precision and sampling control in RBFE comparisons by optimizing distance restraint selection.
• Enveloping Distribution Sampling and Multi-Site Dynamics: Provides restraint sets compatible with EDS and multi-site dynamics for exploration of complex free-energy landscapes.

Methodology:

Uses a graph-based methodology with geometric measures and a greedy selection algorithm, combined with automated categorization of system representations, to select distance restraints.