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B.A., Thiel College
Ph.D., Purdue University
My areas of interest are in computational chemistry and biophysics. Specifically, my research group develops and applies computational methods to study the dynamics, structure, function and reactivity of small molecules, proteins, polymers, and enzymatic reactions. We are currently working in the following areas: • Application of molecular mechanics and dynamics to study the structure/function of proteins interacting with surfaces.
• Study of substrate-receptor interactions using a variety of computational tools, such as Free Energy methods, Brownian dynamics, comparative modeling, docking, and Poisson-Boltzmann electrostatics.
• Application of quantum mechanical calculations to understand the reactivity of nitrile anions and electronic structure of nanoclusters, e.g. peptide capped CdS.
• Development of new and novel software programs that can be used in the above research projects.
• Ice crystal growth is responsible for cellular/tissue damage within biological materials. Inhibitors or modifiers of ice crystal growth, analogous to the functional behavior of native antifreeze polypeptides, need to be developed for this and for other possible cryoprotectant roles. Examples of industrial applications include improved storage of frozen foods, increasingly frost-tolerant plants, airplane fuel and wing de-icers, and better blood preservation methods. Gross identification of adsorbing ice faces has been done (Knight et al., 1991). Follow-up studies are now needed to yield more detailed molecular information on molecule-surface interactions and on the rates of adsorption/desorption as a function of ice face. In order to understand and evaluate the effectiveness of both native and synthetic polypeptides with respect to their ability to inhibit and/or modify the growth of the ice crystals at ice interfaces, interrelated theoretical and experimental work is needed. To gain a molecular insight into the interactions of the antifreeze proteins (AFP) at the ice/water interface we are investigating the mechanism(s) of protein-ice interactions through computational analysis and modeling studies.
• Membranolysis is the breakdown of lipid bilayer which is used to define a cell or organelle. In this particular case we are studying the influence of materials such as inorganic crystals and ice in the presence of lipid bilayers. Our studies are using the results from molecular dynamics simulations and electrostatics calculations to determine the intermolecular forces responsible for bilayer breakdown.
• One project is the study of glycosyl hydrolases that cleave chitin and chitin-like polymers into smaller saccharides. We are applying computational chemistry methods coupled with molecular and structural biological techniques to study Chitinase A and other members of the same chitolytic family. We are studying the binding of polysaccharides to Chitinase A using molecular mechanics (MM) and dynamics (MD). The catalytic reaction mechanism is being studied quantum mechanically (QM) as well as by using a hybrid QM/MM method.
• A second project being conducted is in the binding of "novel" substrates to receptors. This work emphasizes the application of current theoretical methodologies such as docking simulations, finite-difference Poisson-Boltzmann (FDPB) electrostatics, free energy pertubation (FEP) and QSAR methods to study the binding strengths and kinetics between known and hypothesized "novel" inhibitors. Current work includes the study of sulfonamide inhibitors of carbonic anhydrase as well as new NNRT inhibitors of HIV-1 reverse transcriptase. This area of research will facilitate the discovery of concepts of broad relevance, in addition to clarifying the mechanisms in binding between a substrate and its receptor.
• A third project in the area of substrate - receptor interactions is in the area of neurotransporters such as dopamine and seratornin transporters. In this project we are using homology modeling techniques to predict three dimensional structures of these transmembrane systems. Once we have a three dimensional structure for these systems we are using current docking software to identify potential binding sites for substrates of these transporters. Based upon the docking results we are suggesting potential mutation experiments and carrying out the experiments with our collaborators in the Mylan School of Pharmacy.
• The first project in this area is the elucidation of the structure and reactivity of nitrile anions. Here we are applying electronic structure methods to understand the role and influence of solvent and counter ions in the structure and reactivity of five and six member rings containing the nitrile anion functional group. The goal of the research is to rationalize, on a molecular level, the experimental results for these systems in which the counter ion and solvent have been varied.
• The electronic structure and optical properties of peptide nanoclusters is not well established. Using electronic structure calculations on experimental nanoclusters we are developing insight into the stability and properties of peptide encapsulated cadmium sulfide and cadmium selenide nanoclusters, sometimes referred to as quantum dots.
• Biomolecule and small molecule - surface systems are by their very nature multiscale problems. That is there are temporal scales that vary from picoseconds to seconds and spatial scales that vary from Angstroms to microns. Therefore to effectively study these types of systems on must perform a multiscale simulation which combines various techniques that best represent the various temporal and spatial components. We have developed a hybrid BD/MD simulation method to cover spatial scales of Angstroms to nanometers and temporal scales from picoseconds to nanoseconds. We have applied this method in our study of quantum dot adsorption to surfaces.
• In the study of water clusters or bulk water one is confronted with issues such as which force field is best, which simulations algorithm is best, and what software has all of the features needed to do state of the art simulations. In collaboration with Professor Ken Jordan from the University of Pittsburgh we are developing highly parallelized molecular dynamics and Monte Carlo software suite to study properties of water from clusters to bulk in which polarization and many body effects are considered.
For more detailed information about my research projects, please visit the JDM Group website .
Office Phone:412.396.6341
Email:mailto: madura@duq.edu |
