Calculation of the binding of small 

 molecules to DNA and other biological 

 macromolecules depends upon a com- 

 plex interaction of electrostatic fields, 

 solvent-accessible surface, and other 

 physicochemical properties. Structure- 

 based drug design is a key biomedical 

 HPCC Grand Challenge. 



3 Developing a "dynamical model" for the structure 

 of proteins essential for the replication of the 

 human immunodeficiency virus 1 (HIV-1), which 

 may help in generating inhibitors of the protein. 



-I Determining the three-dimensional structure of 

 proteins by developing algorithms that model how 

 proteins fold based on their amino acid 

 sequences. 



□ Modeling the ability of molecules to bind to target 

 receptors in solution by calculating their "solvation 

 energies." This is a crucial component of rational 

 drug design. 



DCRT developed parallel methods for the following 

 biomedical applications: 



-"The three-dimensional reconstruction of herpes 

 virus images from two-dimensional projections of 

 the virus obtained from electron micrographs. 



-"The calculation of the solvent accessible surface 

 area of proteins that is used to predict the confor- 

 mation of these molecules. 



3 The generation of primary sequence patterns from 

 sets of related protein sequences contained in a 

 database. 



-J The within-subject registration of PET (Positron 

 Emission Tomography) images for the correction 

 of roll, yaw, pitch, and translation. 



-"The processing of NMR (Nuclear Magnetic 

 Resonance) spectroscopy data using the 

 Maximum Entropy Method for determining the 

 structure of proteins. 



-"Ab initio quantum mechanical calculations for 

 molecules of biological interest. 



-"Molecular dynamics calculations with a parallel 

 implementation of CHARMM, a molecular model- 

 ing program that takes atomic coordinates of 

 molecules and renders graphical images of those 

 molecules that can be manipulated in various 

 ways for experimental chemistry. 



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