TITLE: Towards All-Electron Modeling of Biomolecular Systems

SPEAKER: Professor Kenneth M. Merz, Jr.

TIME: Tuesday Mar. 26, 2002 at 4 PM

PLACE: George P. Williams, Jr. Lecture Hall, (Olin 101)

With the explosion in the availability of high-resolution X-ray structures of biomolecules there is an ever increasing need to annotate this structural data in order to extract, for example, information regarding the folding of these molecules as well as their interactions with small-molecule therapeutics and their environment(s). In this presentation, we will argue that quantum mechanics is now able to annotate available biomolecular structures in unique ways. In order to support this notion we will des cribe our recent efforts at applying semiempirical linear-scaling methodologies to biological systems. First, we will briefly discuss the divide and conquer approach (D&C) as applied to semiempirical theory at the NDDO level (i.e., MNDO, AM1 and PM3). We will also demonstrate the performance of the method and discuss its range of applicability to biological macromolecules. In particular, we will focus on applications that examine charge transfer effects at the biomolecule/water interface. In order to begi n to widely apply semiempirical linear-scaling methodologies to biological systems solvent must be included in the calculations. Thus, we will describe the implementation and application of Poisson-Boltzmann (PB) methodologies that use charge distribution s determined using these quantum mechanical methodologies. The final topic will cover the development of a Quantum Bioinformatics Database (QBD) that is capable of storing and retrieving quantum mechanically derived information (e.g., charge distributions , MOs, total energies, etc.) regarding biomolecules and then analyzing this data in biologically meaningful ways.