Automated Topology Builder (ATB)

Automated Topology Builder (ATB) generates molecular topologies and force-field parameters to support development and application of molecular force fields in Molecular Dynamics and Monte Carlo simulations of biomolecular systems.

Key Features:

• Molecular topology and parameter generation: Produces topologies and force-field parameters for use in Molecular Dynamics and Monte Carlo simulations of biomolecular systems.
• Biomolecule–ligand modeling: Provides parameters suitable for modeling biomolecule–ligand complexes.
• Free energy calculations: Supplies parameter sets compatible with free energy calculations.
• Structure-based drug design support: Enables molecular simulations that inform structure-based drug design.
• X-ray crystal structure refinement: Facilitates refinement of x-ray crystal structures via parameterized molecular models.
• Integration with ASP algorithm: Integrates the amphipathic structure prediction (ASP) algorithm for peptide structure prediction.
• ASP evolutionary approach: Uses an evolutionary approach to predict three-dimensional configurations of α-helical membrane-active antimicrobial peptides (AMPs).
• Amphipathicity optimization: Optimizes amphipathicity to predict peptide structures at the water-membrane interface and to distinguish curved versus linear peptide conformations.
• Membrane-mechanism context: Accounts for AMP mechanisms including barrel-stave and toroidal pore formation and micellization via a carpet mechanism.

Scientific Applications:

• Modeling biomolecule–ligand complexes: Supports simulation-based studies of biomolecule–ligand interactions.
• Free energy calculations: Enables parameter-driven free energy estimation for binding and conformational studies.
• Structure-based drug design: Provides parameter sets that assist in structure-based drug design workflows.
• X-ray crystal structure refinement: Aids in refining x-ray crystal structures through molecular modeling.
• AMP structure and mechanism prediction: Predicts α-helical membrane-active AMP 3D configurations and distinguishes curved versus linear conformations relevant to membrane interaction mechanisms.
• Therapeutic and antimicrobial research: Informs therapeutic applications and drug design strategies targeting microbial infections by elucidating AMP–membrane interactions.

Methodology:

Generates molecular topologies and force-field parameters for Molecular Dynamics and Monte Carlo simulations; integrates the ASP algorithm, which employs an evolutionary approach and optimizes amphipathicity to predict three-dimensional configurations of α-helical membrane-active AMPs at the water-membrane interface and to distinguish curved versus linear conformations.