A grant has been awarded to Mississippi College (MC) under the direction of Dr. David Magers for the acquisition of a 32-processor Beowulf cluster and integrated parallel computational chemistry software for the calculation of conformational energetics and molecular parameters of a series of biologically significant molecules. All biochemical reactions require the formation of stable complexes between the molecular participants. Thoroughly understanding the physical basis for the recognition of small molecules by protein and nucleic acid targets requires a detailed knowledge of both molecular structure as well as the thermodynamics which describe the strength of the binding interactions. It is well recognized that the structures of the reactants and the solvent dictate these binding energetics. However, it is still not possible to predict precisely the binding affinity of small molecules to their cognate protein or nucleic acid targets.
With the advance of multi-processor computers running in parallel, it is now possible to treat small molecules rigorously by density functional theory and ab initio methods. Specifically, the Beowulf cluster and integrated software acquired through the grant will be used to examine the quantitative relationships that exist between the structure and the binding thermodynamics of a small library of novel naphthylquinolines that specifically recognize triple helical DNA structures. These structures such as H-DNA are currently thought to help regulate gene expression since they have been found to occur in the promoter regions of some mammalian genes. High level quantum mechanical calculations will be used to predict the molecular properties of these naphthylquinolines and then to correlate them to experimentally determined binding energetics.
The Committee on Professional Training of the American Chemical Society, which sets the guidelines for accredited undergraduate chemistry programs recently announced updated guidelines recognizing the increasing importance of computers in chemistry. Computational laboratory assignments have already been added to several courses at MC, and the third semester course in Physical Chemistry is designed exclusively around theoretical and computational chemistry. The new computer will have a direct impact on the computer assignments in these courses allowing larger and biologically relevant systems to be investigated. Finally, the Beowulf cluster will increase MC's overall research infrastructure and broaden the possibilities for collaboration with nearby colleges and universities.
