Proteins play a central role in cellular function and are ultimately the mechanism through which many diseases have their effect. Increasingly the design of drugs to treat such diseases is based on a detailed understanding of protein structure and its interaction with small drug molecules. Computational structural biology is concerned with the modeling and computer simulation of structure, function and dynamics of biological molecules. The NIH Research Resource in Structural Biology brings together a multidisciplinary group of researchers in Biophysics, Computer Science, Biochemistry and Mathematics to develop and apply new modeling and simulation techniques.

There are many computational challenges within the larger effort, but computer simulation of molecular dynamics (behavior over time) is one in which Computer Science is most closely involved. Such simulations require a tremendous amount of computation because the basic simulation timestep is very small compared to the time-scale of the behaviors of interest. The challenge is to increase the simulation rate, and to provide the possibility of "steering" the simulations toward interesting phenomena by interacting with a visualization of the running simulation.

• To accelerate molecular dynamics simulations we are designing new parallel algorithms and are concentrating on their high-performance implementation on parallel computers with a potentially large number of processors.
• To provide computational steering of molecular dynamics simulations we are constructing the SMD system which provides a graphical interface to the dynamics simulation, through which we may introduce additional restraints into the simulation to effect, for example,the extraction of a ligand from a protein.

• Analytical and experimental observations show that the performance of parallel algorithms using spatial decomposition for truncated interaction molecular dynamics simulations is more dependent on load balance than communication efficiency on modern parallel computers. A performance model was used to explore several decomposition methods and to choose among them.
• The SMD system is being used to help find the exit pathway through which Xenon can enter and exit a hydrophobic cavity in the T4-Lysozyme.
• Recent publications

• Faculty Jan Hermans (PI, Biochemistry and Biophysics), Lars Nyland, Jan Prins
• Current students: Geoff Mann (Biophysics), Previous students: Jon Leech, James Chen, Michael Lappe

• National Institutes of Health National Center for Research Resources.
• National Science Foundation Grand Challenge Application program.
• Intel Corporation Education 2000 equipment grant.

• UNC Computational Structural Biology main page.
• NIH project home page.