Ian S. Haworth, PhD
Associate ProfessorPharmacology and Pharmaceutical SciencesCurriculum Vitae
- Computer modeling of biomolecular structure
- Design of biomolecular interfaces through new algorithm development
- Incorporation of solvation into molecular docking algorithms
Ph.D., University of Liverpool, U.K.
The focus of my laboratory is the design and implementation of new computer algorithms for pharmaceutical and biochemical research. Our particular interests are in establishment of methods for structure determination based on indirect experimental information and development of knowledge-based based methods for prediction of biological interfaces.
In the first of these areas, we have developed tools for structure determination of proteins, RNA and DNA based on input from EPR spectroscopy. Of particular importance, we have been able to obtain structural information for two lipid-bound proteins and an amyloidogenic aggregate that were difficult to study using other biophysical techniques. We have developed methods for computation of inter-spin label distances (PRONOX, NASNOX, ALLNOX, FOLDNOX) for use in experimental planning for EPR DEER experiments. We have also developed methods for conversion of DEER data into molecular structure. This has resulted in the first publication of an atomic level structure of a protein (alpha-synuclein) buried in a vesicle lipid bilayer. We have also used these methods to determine a close-to-atomic resolution structure of a protofilament of islet amyloid polypeptide (IAPP). Using a new algorithm (MFIBRIL), we have been able to develop this structure into a model of the complete IAPP fibril. This model will serve as a valuable target for diagnostic and therapeutic design.
In our knowledge-based design work, we have focused on solvation of biological interfaces through development of an algorithm for positioning of water molecules at interfaces. This has many implications for therapeutic design. We have generated an algorithm for efficient solvation of biomolecular interfaces. The WATGEN algorithm has facilitated a deeper understanding of the details of solvation that mediate protein-protein and protein-small molecule interactions. This understanding is a key aspect in rational drug design, since it allows specific water molecules to be identified for displacement through ligand modification. Our current work is aimed at rapid computation of the energetics of water molecules at interfaces. This algorithm is freely available for academic use.
Ph.D., University of Liverpool, U.K. (advisor: Prof. Raymond J. Abraham), 1986-1989, Physical Organic Chemistry. Postdoc. Oxford University, U.K. (advisor: Prof. W. Graham Richards), 1989-1992. Joined USC in 1992. Dr. Haworth's research interests lie at the interface between chemistry, biology and the computational sciences, with the goal being an improved understanding of the dynamics of molecular association of nucleic acids and proteins. Dr. Haworth has published over 80 papers in this area, and the work has attracted funding from federal and non-federal sources.
Dr. Haworth's laboratory has developed algorithms for protein-peptide interface solvation, prediction of MHC-peptide-TCR association, solvation-based molecular docking, nucleic acid structure building, and aptamer design. The goal of these algorithms is accurate reproduction of molecular association, through proper molecular and theoretical descriptions of biological interfaces.
Dr. Haworth is also currently the Director of Curriculum for the Pharm.D. program in the School of Pharmacy. In this role, he has been responsible for major recent revisions in the Pharm.D. program. Dr. Haworth has also been active in moving some of the basic science Pharm.D. curriculum from a lecture/examination approach to a more learner-centered, case study-based approach, and has published a number of articles in this area.