Computational Chemistry

Computational Chemistry and Computational Biology at the University of Kentucky R. Michael Sheetz, PhD Center for Computational Sciences

- Computational Chemistry The University of Kentucky occupies a unique position within the computational chemistry community. Our university is the designated site for computational chemistry within the National Computational Science Alliance (Alliance) - a group of university, government, and industry researchers working together to develop an advanced, national computational infrastructure for scientific computing. University of Kentucky

- Computational Chemistry As a national site for computational chemistry, we have the opportunity to provide computing resources for research covering a very diverse set of areas and topics involving computational chemistry including atmospheric & environmental chemistry  physical organic chemistry biological chemistry materials science University of Kentucky

Computational Chemistry Atmospheric and Environmental Chemistry University of Kentucky

Computational Chemistry Atmospheric Degradation of Isoprene University of Kentucky

Computational Chemistry Atmospheric and Environmental Chemistry Although our level of understanding of the biogeochemistry cycles of greenhouse gases, oxidants, and aerosols has increased substantially during the past 5 - 10 years, our understanding of the these cycles is far from complete. One very important greenhouse gas is tropospheric ozone. The behavior of this gas is extremely complex and is highly correlated with the efficiency of atmospheric oxidation ( [OH] ). University of Kentucky

Computational Chemistry Atmospheric and Environmental Chemistry Consequently, a much better understanding of the pathways for synthesis and degradation of ground-level ozone is a topic of considerable interest in atmospheric/environmental chemistry. Sources of tropospheric ozone include: stratospheric ozone in situ photochemistry in the atmosphere emission of volatile carbon by natural resources University of Kentucky

Computational Chemistry Atmospheric and Environmental Chemistry The single most important volatile carbon contributing to ground-level ozone synthesis is isoprene (2-methyl-1,3-butadiene) In daylight, reaction with OH is the primary initiator of isoprene degradation in the atmosphere. University of Kentucky

Computational Chemistry Atmospheric and Environmental Chemistry In the presence of NOx , atmospheric decomposition of isoprene produces a wide variety of degradation products OH, NOx isopreneformaldehyde methyl vinyl ketone methacrolein 3-methylfuran organic nitrates a large variety of carbonyl compounds University of Kentucky

Computational Chemistry Atmospheric and Environmental Chemistry The variety of carbonyl products formed in the decomposition of isoprene has hampered the identification of these products and their yields and has made the elucidation of the pathways for degradation of isoprene in the atmosphere extremely difficult. One of the current computational chemistry projects being carried out at our facility is an investigation of the atmospheric degradation pathways of isoprene. University of Kentucky

Computational Chemistry Atmospheric and Environmental Chemistry Following reaction of isoprene with OH, six alkoxy radicals are initially formed. In this current study, the converged structures, vibrational frequencies, and energies of all six alkoxy radicals as well as for the transition states and products for all C – C bond fission pathways that can conceivably occur in the atmosphere is being determined using density function theory (DFT) . University of Kentucky

Computational Chemistry Atmospheric Oxidation of NOx University of Kentucky

Computational Chemistry Atmospheric and Environmental Chemistry The chemistry of nitric oxide (NO) is of considerable significance as a reactive atmospheric NOxspecies. The direct oxidation of NO by O2 to give nitrogen dioxide (NO2) 2NO + O2 2NO2 is thought to play a critical role in processes such as combustion, and can contribute to atmospheric chemistry under conditions of high NO concentration, such as in emissions from power plants or automobiles. An unusual peroxide, ONOONO, has been proposed as an intermediate in this oxidation reaction. University of Kentucky

Computational Chemistry Atmospheric and Environmental Chemistry One of the projects carried out at our facility was an investigation of the O  O bond breaking reactions of this unusual peroxide using CBS-QB3 and B3LYP/6-311G* hybrid density functional theory. The results of this investigation showed that the cis-oriented NO2 correlates electronically with the 2A1 ground state whereas the trans-oriented NO2correlates electronically with the 2B2 excited state  providing an unusual example of conformation-dependent electronic state selectivity. University of Kentucky

Computational Biochemistry University of Kentucky

Computational Chemistry Catalytic Mechanism of Superoxide Dismutases University of Kentucky

Computational Biochemistry The superoxide dismutases (SODs) of E. coli and nitroreductase (NR) from E. cloacae serve as two mutually complementary systems in which to study fundamental aspects of enzymatic redox catalysis biochemical defenses against oxidative damage mechanisms of waste detoxification University of Kentucky

Computational Biochemistry Redox enzymes combine the reactivity and versatility of transition metal ions and conjugated cofactors with the specificity and selectivity of enzymes. These enzymes catalyze chemical reactions as energetically demanding as the reductive cleavage of N2(the second strongest bond known), yet this reduction occurs under relatively mild conditions within the interior of a protein. University of Kentucky

Computational Biochemistry A primary area of interest in physical biochemistry is how proteins activate bound cofactors for specific reactions, control them so that other reactions are minimized, and manage to evade irreversible reaction with the cofactor themselves. One of the current projects in computational biochemistry being conducted at our facility is an investigation of the mechanisms by which proteins determine the redox potential and reactivity of bound flavins. University of Kentucky

Computational Chemistry Catalytic Mechanism of ODCase University of Kentucky

Computational Biochemistry The formation of uracil ribose 5’-monophosphate is the final step in the de novo synthesis of pyrimidine nucleotides. The reaction involves the decarboxylation of orotidine 5’-monophosphate and is catalyzed by the enzyme orotidine 5’-monophosphate decarboxylase(ODCase). This reaction requires neither a cofactor or a metal ion for activity. O O ODCase NH NH N N - O2C O H+ CO2 O ribose-P ribose-P University of Kentucky

Computational Biochemistry A proposed mechanism for ODCase catalysis involves proton transfer to either the 2-oxygen (O2) or the 4-oxygen (O4) to promote decarboxylation of the orotate moiety. One of the projects in computational biochemistry conducted at our facility investigated this proposed mechanism for the decarboxylation of orotate. University of Kentucky

Computational Biochemistry The computational chemistry calculations from this investigation suggests that O4-protonation of orotate followed by decarboxylation is preferred energetically over O2-protonation the mechanistic basis for the more favorable energetics of O4-protonation is a greater basicity of the 4-oxygen over the 2-oxygen in the transition state of orotate University of Kentucky

Computational Biochemistry Conformation of Proline-Rich Polypeptides University of Kentucky

Computational Biochemistry Proline-rich regions of peptides are believed to adopt an extremely flexible left-handed polyproline II (PPII) helical conformation in solution. However, it is not clear from experimental studies that this is actually true. One of the projects in computational biochemistry currently being conducted at our facility is an investigation of the conformations adopted by proline-rich peptides and the determinants of a PPII helical conformation in solution. These studies are being carried out using a combination of molecular dynamics and Monte Carlo simulation. University of Kentucky

Computational Biochemistry Repair of Damaged DNA University of Kentucky

Computational Biochemistry DNA damage is responsible for a number of diseases including various forms of cancer. Another project in computational biochemistry currently being conducted at our facility is an investigation of the differences in dynamics and conformations of damaged and undamaged DNA and their interactions with DNA repair proteins. The studies that are being carried employ molecular dynamics simulation with the incorporation of dynamic information from NMR spectroscopy. University of Kentucky

Materials Science University of Kentucky

Computational Chemistry and Materials Science Magnetism in Non-Metallic Molecular Materials (A combination of computational chemistry and condensed matter physics) Certain 2-dimensional C60 structures have been found to exhibit spontaneous magnetization that continues to exist far above room temperature. Two mechanisms have been proposed to explain how this magnetization originatesin these non-metallic materials : unpaired electrons donated by edge carbon atoms vacancies within the polymeric carbon University of Kentucky

Computational Chemistry and Materials Science Magnetism in Non-Metallic Molecular Materials Both mechanisms entail the transformation of sp2 to sp3 orbitals in combination with some type of structural rearrangement of the polymer. One of the current projects in computational chemistry being conducted at our facility involves an investigation of the interplay between structural defects and sp3 hybridization in explaining the origin of the observed spontaneous magnetization in these carbon polymers. University of Kentucky

Computational Biology University of Kentucky

Computational Biology The characterization of DNA and protein sequences is a problem of continually increasing importance in biology, biochemistry, medicine, and pharmacology. The most commonly used procedure employed in such investigations involves the rapid screening of large databases of DNA and protein sequences. The most widely used tool for screening of these databases is BLAST (Basic Local Alignment Search Tool). Most commonly, these applications are run as serial searches on a single computer processor. University of Kentucky

Computational Biology Unfortunately, the continual input of sequence information into these databases has resulted in an exponential growth in the sizes of these databases. The result has been that single processor searches are becoming extremely inefficient for many sequence investigations. Recently, a parallel implementation of BLAST has been developed that dramatically accelerates the search of large sequences databases. This application, called TurboBLAST, is currently installed on our supercomputer and is scheduled to begin testing by local users in the very near future. University of Kentucky

email address: rmshee0@email.uky.edu University of Kentucky

Computational Chemistry