Conformations and Thermodynamics of Polypeptides
Organization: Army High Performance Computing Research Center (AHPCRC)
Location: US Army Medical Research Institute of Infectious Diseases (USAMRIID),
Frederick, MD
Background:
The use of biological toxins for the purpose of developing new and sophisticated biological
warfare weapons is of great concern. To counter this threat, the US Army is seeking to develop
and to apply computational tools that rapidly generate complex protein structures and analyze
physical properties. The goal is use this information to develop suitable protective drugs and/or
antidotes.
The methods of Monte Carlo simulated annealing (MCSA) and metropolis Monte Carlo (MMC)
were successfully employed in protein structure prediction calculations and in calculations of
thermodynamic properties of proteins, respectively. Computed data that agreed with experiment
were the physical properties of two 7-residue neuropeptides that differ by a single amino acid,
and the prediction of a 12-residue protein surface loop that interacted with 4 buried water
molecules in the X-ray crystal structure. The prediction calculations relied on multiple
independent MCSA conformational search runs starting from random conformations to populate
the multiple minimum (or macrostates) on the potential energy surface. The macrostates were
ranked based on accurate thermodynamic data obtained from room temperature MMC
calculations and clustering analyses.
Objective:
Our goal is to dock small molecule inhibitors and / or peptide inhibitors on the catalytic domain
of Botulinum neurotoxin and score and rank the poses.
Pre-requisites:
Undergraduate courses in Calculus, Physics and Chemistry are required. Knowledge of protein
structure, unix operating system, computational chemistry, and molecular visualization and
modeling software are very useful.
Number of Academy Cadets/Midshipmen: 1-2
Requested duration: 3-4 weeks
Security Clearance required: NAC
Contact:
Louis Carlacci, Ph.D., AHPCRC / Network Computing Services, Inc.
Ph. 301-619-6732
e-mail: lcarlacc@ahpcrc.org
Date 2/12/16
Date 2/12/16