AMMOS

AMMOS performs atomic-level energy minimization of protein–ligand complexes using the AMMP sp4 force field to refine structures and evaluate minimized binding energies.

Key Features:

• Atomic-Level Energy Minimization: Uses the physics-based AMMP sp4 force field to optimize protein–ligand complexes at atomic resolution.
• Receptor Flexibility Levels: Implements five levels of receptor flexibility, ranging from rigid to full-atom (partial to full atom) flexibility during optimization.
• Explicit Water Molecules and Metal Ions: Incorporates explicit water molecules and individual metal ions into the optimization process.
• Computed Energies and Ligand Ranking: Calculates minimized binding energies and ranks ligands based on those energies.
• Interactive Visualization and Analysis: Provides interactive visualization of refined complexes alongside comprehensive analysis of computed energies.

Scientific Applications:

• Virtual Screening: Supports structure-based in silico ligand screening by refining docked complexes and re-evaluating binding energies.
• Structural Optimization: Refines 3D structures of small molecules within chemical libraries to improve suitability for docking studies.
• Receptor Flexibility/Induced-Fit Considerations: Accounts for receptor dynamics through partial to full-atom flexibility during minimization, aiding induced-fit modeling.
• Enrichment Studies: Improves enrichment of active compounds in post-docking minimization by increasing the proportion of known inhibitors recovered in top-ranked subsets.

Methodology:

Initial complex preparation from experimental or modeled protein–ligand structures; energy minimization using the AMMP sp4 force field with five levels of receptor flexibility and optional inclusion of explicit water molecules and metal ions; computation of minimized binding energies and analysis/visualization of refined complexes.