Cluster Activity

Justification

Both computer-aided molecular design and bioinformatics techniques continue to be important for fueling biotechnology advances. These studies help visualize target structures and engineer desired changes in them. Refined knowledge of targets that emerges from such computational techniques can lead to enhanced information about protein-protein, protein-nucleic acid and protein-ligand interactions that are necessary for such strategies as targeted gene therapy or RNA-interference based therapeutics. Computational time for the atomistic simulations frequently required by such computational problems is significant. This is the reason why compute-intensive applications represent significant bottlenecks in the pipeline for many companies and labs. A resource such as the BSBC lab available here can, therefore, greatly stimulate biotechnology research in the region.

In the sections below, projects from UNCG faculty, as well as, projects from Targacept are described. Additional projects from our sister institution, NC A&T are also included here. The projects illustrate the range of relevant problems that can be addressed using the HPC cluster requested in this application. Projects include protein design projects to support targeted gene therapy for chronic pain; fundamental studies aimed at the improvement of RNA-interference-based therapeutics; biomolecular simulation projects aimed at a fundamental understanding of ligand interaction and activation of neuronal nicotinic receptors; reaction trajectory simulations of reductive activation of transcription factor NF-κB; and, molecular mechanics/dynamics studies of enzyme/substrate interactions in Orotidine-5’-O-monophosphate decarboxylase. Fundamental computer algorithim development projects for biomolecular simulation are also proposed. These include projects to develop the next generation molecular mechanics force field, as well as, a project to develop Rosetta-like ab initio protein folding tools 2, 3 to model with high resolution, hypothetical proteins from genome sequencing projects.

BSBC Projects

• Patricia H. Reggio, UNCG
  Novel Targeted Gene Therapy Using Engineered Mu Opioid Receptors to Treat Pain
• E. W. Taylor, UNCG
  Molecular modeling and Simulation Research Projects from the Laboratory for Molecular Medicine (LMM), Office of Research
• Phil Hammond, Targacept
  MD Simulations of Neuronal Nicotinic Receptors
• J.Philip Bowen, UNCG
  Molecular Mechanics Development
• Yaohang Li, NC A&T
  Deciphering Structures of Hypothetical Proteins via High-Resolution ab initio Structure Prediction
• Divi Venkateswarlu, NC A&T
  Structural Basis of Blood Coagulation Cascade: Characterization of Serine Protease Enzyme-Substrate Complexes and Development of Exosite-Based Inhibitors