Probing biomolecular systems in atomic detail requires specilized software tools. The computational tools we have assembled employ advanced molecular dynamics simulation techniques, such as replica exchange and biased samplings [1], in an HPC environment. These tools can be applied to screen vaccine candidates or to design antibacterial drugs based on antimicrobial peptides.

Vaccine candidate screening

This application supports replica-exchange molecular dynamics (REMD) simulations [1] of vaccine candidates using the Multiscale Modeling Tools for Structural Biology (MMTSB) [2]. Implicit solvent models are used to model solvation. Thermal property profiles are calculated by the weighted histogram analysis method [1] and can be used to screen vaccine candidates for thermal stability.

Membrane insertion of peptides

These software tools calculate membrane-insertion profiles of peptides from REMD simulations as implemented by customized MMTSB tool set components. Membrane and solvent are described implicitly by a generalized Born implicit solvent/membrane model. If necessary, peptide positions are restrained with respect to the membrane center to sample sufficient peptide conformations across the membrane interface in order to calculate the free energy of their insertion into the membrane. These software tools can be used to design antimicrobial peptides with specific membrane-insertion profiles.

The tools are currently deployed on jaws at the Maui High Performance Computing Center, and on mjm and jvn at the Army Research Laboratory's Major Shared Resource Center.