DUKE University

Algorithms for Protein Design and Drug Design


Some of the most challenging and influential opportunities for Physical Geometric Algorithms (PGA) arise in developing and applying information technology to understand the molecular machinery of the cell.  Our recent work (and work by others) shows that many PGA techniques may be fruitfully applied to the challenges of computational molecular biology. PGA research may lead to computer systems and algorithms that are useful in structural molecular biology, biophysics, proteomics, and rational drug design.


Concomitantly, a wealth of interesting computational problems arises in proposed methods for discovering new pharmaceuticals.  In this talk, I'll discuss some recent results from my lab, including new algorithms for protein design and drug design.  Protein redesign aims at improving target protein properties, such as increasing the stability, switching an enzyme's specificity towards a non-cognate substrate, or redesigning the protein so that it will perform a completely novel function. Exhaustively testing protein mutations in vitro is infeasible, due to the enormous size of the space of possible mutations. Computational (in silico) approaches can efficiently and accurately explore the combinatorial space of candidate solutions, and have proven valuable for protein redesign and protein engineering.


I'll discuss new results, and survey some of the algorithmic and computational challenges.  Finally, I will describe experimental results from applying our algorithms to redesign an antibiotic-producing enzyme, and to design allosteric small molecule inhibitors of protein:protein interactions that play a critical role in the development of acute myeloid leukemia and acute lymphocytic leukemia.



Bruce Donald is the William and Sue Gross Professor of Computer Science at Duke University, and Professor of Biochemistry in the Duke University Medical Center. He was an assistant and associate professor in the Computer Science Department at Cornell University from 1987-1998.  Donald received a B.A. from Yale University, and a Ph.D. in Computer Science from MIT.  He has been a National Science Foundation Presidential Young Investigator and was awarded a Guggenheim Fellowship for his work on algorithms for structural proteomics.



B17 Upson Hall

Thursday, September 18, 2008

Refreshments at 3:45pm in the Upson 4th Floor Atrium

Computer Science


Fall 2008