COMPUTATIONAL STUDIES OF BIOMOLECULAR SYSTEMS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of the research in our lab is directed towards the understanding of the structural, dynamic and energetic basis for biological function. The work in our laboratory encompasses molecular simulations and computational studies of several biological systems. 1. We investigate the aggregations properties of mixed membranes composed of neutral and negatively charged lipids. Molecular and FEP simulations are used to assess the fundamental energetic basis for lipid aggregation and the energetics of protein association with lipids. 2. We study the molecular basis of PIP2 regulation of inward rectifying K-channels. Brownian dynamics simulations identified the sites of PIP2 binding on the channel and MD simulations of the tetramer in phospholipid membrane are used to define the dynamics and energetics of PIP2-induced channel opening. 3. The selectivity of autoimmunogenic peptides with Major Histocompatibility Complex (MHC) proteins is studied by simulations and free energy methods. The role of water in the association of the peptideMHC complex with the T-cell receptor is investigated by Grand Canonical Monte Carlo simulations. 4. MD simulations are used to define the basis for allosteric regulation of factor VIIa - a serine protease important in the blood coagulation pathway. Combined essential dynamics is used to identify the structural and energetic basis for allosteric activation and inhibition. 5. Homology modeling of sweet taste receptors produced models that are used in docking and simulations. These studies predicted the binding pockets in the extracellular and transmembrane domains that were tested by experimental techiniques.