Simulation, Analysis, and Mathematical Modeling
The Simulation, Analysis, and Mathematical Modeling (SAMM) group maintains expertise in Computational Chemistry; from modeling full proteins, examining protein-ligand interactions, predicting absorption and emission spectra from fluorescent proteins, calculating low-energy conformations of flexible nanoparticles, and accurately determining reaction profiles for the formation and release of drugs in cancer research. The SAMM group maintains extensive mathematical expertise and has applied it to QSAR investigations, GWAS analysis, predicting protein interaction networks, quantitative proteomics, and biomarker discovery. The SAMM group is also responsible for the contents of the Collaboratory for Structural Nanobiology website. As such, the group is working to refine images obtained by electron microscopy and model the physical properties of nanoparticles to predict their toxicity.
Theoretical Study of Electronic Mechanisms and Energetics of NO- and HNO- Releasing Chemotherapeutics
In support of the Laboratory of Chemical Carcinogenesis, we have developed a novel quantum chemistry technique to extract and exhibit clearly the electronic interactions responsible for the chemical properties of a system. This procedure, termed Intrinsic Localized Density Analysis (ILDA), expresses a complex quantum chemical wave function in terms of interactions between atomic-like orbitals thereby providing simpler, and conventional descriptions of the inherent bonding interactions. We are applying this technique for the study of the electronic properties of a novel class of molecules known as diazeniumdiolates. These systems are distinct in that they are capable of releasing nitric oxide (NO) and/or nitroxyl (HNO). As such, they have significant potential as beneficial biological agents. The release of NO involves the simultaneous breaking of single and double nitrogen-nitrogen bonds.
Theoretical Investigation of the Wild-Type Green Fluorescent Protein (wt-GFP) Chromophore and Related Derivatives
The wt-GFP protein occurs naturally in the jellyfish Aequorea victoria and fluoresces bright green light upon absorption of blue light. It has been established that the fluorescence properties of wt-GFP arise primarily from its central chromophore. The wt-GFP gene and its mutations, which emit various colors, are widely used in cellular and molecular biology as expression reporters and biosensors. A key to effective utilization is the design of mutants that have desired absorption and emission properties. In this respect, it is vital to determine the electronic structures that give rise to the observed spectra, and to be able to predict their electronic properties accurately.
Role of IL-22 as a survival factor in cancer
In collaboration with the laboratory of Howard Young, we are presently investigating the role of IL-22 as a survival factor in cancer. Modeling studies have been carried out modeling to understand how IL-22BP12 might be able to mimic the role of IL-22R1 [natural receptor for IL-22]. Based on the binding interface, mutation experiments were proposed and Dr. Young’s lab is currently following up on these predictions.
Structural Annotation of Nanobiomaterials – CSN
Research in Nanobiotechnology deals with problems related to the design, creation and characterization of materials, devices, and systems at the nanometer (1 to 100 nanometers) scale for their application in biomedical devices. The unusual properties of nano scale devices are exploited in biomedical applications in drug delivery, imaging and the treatment of illness at the cellular level. The success of nanobiotechnology hinges on the ability to characterize, predict, and control the biological properties of nanobiomaterials. The Collaboratory for Structural Nanobiology (CSN) is a collection of IT services designed to satisfy the constraints imposed by the molecular characterization of nanobioparticles.
Software Development Efforts