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Curt M. Breneman Research Group

Curt M. Breneman Research Group

wire frame depicting molecule electron density

Breneman Research

Our group's research focuses on understanding and modeling the relationships that exist between molecular structure and function. The highlight of our research is the invention of an entirely new kind of molecular modeling called the Transferable Atom Equivalent (TAE) method. The TAE method allows accurate reconstruction of electron density distributions for very large numbers of drug-sized molecules, or for a few very large protein-sized molecules in a short time frame. Small molecule electron densities can be reconstructed with great speed, enabling large databases to be scanned for desirable combinations of electronic properties in a short period of time. The results of the reconstruction efforts yield sets of electron density-derived molecular property descriptors, as well as atom-centered multipolar representations of molecular electrostatic potential fields.

Our team’s work in TAE modeling has received international attention from research groups and pharmaceutical companies, and is being developed through contributions from the NSF, GE, Millennium Pharmaceuticals, ICAGEN Pharmaceuticals, Pfizer Global Research and the Eastman Kodak Company. We are now applying TAE to problems in large and small molecule binding, protein binding site selectivity, and drug design QSAR modeling. Since the TAE method has allowed the development of an entirely new kind of QSAR/QSPR electronic property descriptors, researchers are exploring the application of these indicators for producing accurate statistical models for many classes of intermolecular interactions. Preliminary results on High Performance Liquid Chromatography (HPLC) capacity factors suggest that the new electronic property indicators are highly correlated with specific modes of molecular binding, and should prove to be of general use in QSAR/QSPR work.

We also were the first to reconcile the controversial issue of how the atomic charges derived from density partitioning are related to the more familiar electrostatic potential-derived charges. In addition, through the use of electron density partitioning methods, this group was the first to show that the conformational preferences of sulfonamides were controlled by the same redistribution of charge and electronic kinetic energy that governs amide stability.










RECCR ©2005 Curt M. Breneman