UTMB

Werner Braun, Ph.D.,
Professor

Faculty

Werner Braun, Ph.D.

About the Lab

The challenge in the post genomic era is to make full use of the vast genomic data in understanding the molecular mechanism of the function of proteins. Funding from the Department of Energy has allowed us to develop an expert system, MASIA, to quantitatively identify motifs and patterns of diversity in protein sequences. MASIA, in combination with homology modeling and molecular dynamics simulations, can be used to characterize functional motifs in protein families. In collaboration with Drs. T. Izumi and S. Mitra from the Sealy Center for Molecular Science (SCMS) we are determining how apurinic/apyrimidinic endonucleases respond to subtle differences in the structure and dynamics of DNA sites damaged by low dose ionizing radiation. We are relating motifs identified by MASIA to the function of DNA recognition, catalysis and protein-protein interaction. Screening gene databases with these novel motifs should reveal new candidates for APE related proteins.

In a different avenue we are developing software tools for determining protein structures by NMR in Structural Genomics Projects. Manual analysis of the thousands of cross peaks in protein spectral data is currently the most time consuming part of protein structure determination by NMR. In a project funded primarily by the NSF, we are developing new software tools to automate and integrate all individual steps in the NMR structure determination process. Our NOAH-DIAMOD suite can interpret NOE data in a fraction of the time that would be required for manual assignment, with equivalent or better resolution. Using this method we determined the 3D solution structure of water borne pheromones from the marine mollusk Aplysia by NMR studies in a project with Drs. G. Nagle and S. Painter (Department of Anatomy and Neurosciences). This structure suggests potential receptor-binding sites of these pheromones and we are examining common functional and structural characteristics of pheromones of other species.

The self-correcting distance geometry based tools we developed for NMR have also proven useful for modeling proteins, as demonstrated by our performance CASP4 and CASP5 competition. We are using our methods to model proteins of medical interest in several collaborative projects. We are determining the structural characteristics of cedar pollen allergens in collaboration Drs. E. Brooks, T. Midoro-Horiuti and R. Goldblum (Department of Pediatrics). We have established 3D-database of allergen structures, SDAP, which combines experimental results and our models for other known allergens. In other projects, we have modeled the structure of proteins involved in apoptosis and other forms of cell lysis.

Interview with Dr. Braun

– by Austin Elam, 2nd year BSCB Student

Dr. Werner Braun was recruited to the University of Texas-Medical Branch (UTMB) to lead the computational biology unit as part of a new center for structural biology. This plan was realized in 1995, and the Sealy Center for Structural Biology has now become an internationally recognized group of faculty in the area of biophysics and structural biology. The biophysical, computational, and structural biology (BSCB) program, which was founded by a group of faculty in the Sealy Center for Structural Biology, brings together talented students from around the globe. This international talent pool for graduate students is one of the many things about the BSCB, Dr. Braun considers as a key element for its success. The BSCB program at UTMB has several attractive features for students as compared to similar graduate programs at other institutions in the country. Dr. Braun commented that, "The medical school environment at UTMB fosters biomedical applications, also in the BSCB program, which is largely rooted in basic sciences. This environment makes the BSCB program unique."

"Newtonian mechanics and the mathematical tools using to derive it is probably one of the most beautiful scientific observation in my opinion because it used mathematics and physics to quantify what man observed in nature. It represented a new level of understanding."– Dr. Braun, discussing his idea of the most significant scientific discoveries.

Dr. Braun indicated that his personal scientific idol would be Albert Einstein, despite the fact that his expertise was in a different area. Importantly, he admires Einstein’s ground-breaking innovations, and he commented that Einstein was always "driven by scientific questions", which is also important for computational biology. When asked what specifically motivates him to do research, Dr. Braun enthusiastically indicated that developing novel structural biology and computational methods for biological applications was most exciting to him.

When asked what he thought was the most beautiful observation in all of science, Dr. Braun stated, "Newtonian mechanics and the mathematical tools used to derive it is probably one of the most beautiful scientific observation in my opinion because it used mathematics and physics to quantify what man observed in nature. It represented a new level of understanding."

While working with Kurt Wüthrich (Nobel Laureate in Chemistry 2002) at the Swiss Federal Institute of Technology in Zurich, Switzerland, Dr. Braun developed new computational methods of 3D protein structure determination by nuclear magnetic resonance (NMR) spectroscopy. At the early stage of protein structure determinations from NMR data, it was not clear if 3D structures of proteins could be solved from NMR data alone. Dr. Braun set the stage for the eventual design and acquisition of 3D structures by NMR. Presently, Dr. Braun’s interests span a broad range of research topics that include the structural biology of allergens, DNA repair mechanisms and virus – cell cell interactions. His group maintains and further develops several Web sites: PCPMer for protein sequence analysis, MPACK for homology modeling of proteins, InterProSurf for prediction of protein interfaces and the Structural Data Base of Allergenic Proteins, SDAP.

Dr. Braun believes that the two qualities most important for graduate students are motivation and educational background. He stated that it is vital that students have an "intrinsic interest" in their research. Dr. Braun’s message to future students and scientists is to always "keep an open mind and never be afraid to try exploring new areas."