The three-dimensional structure of the human immunodeficiency virus (HIV) gag product p24 is to be determined crystallographically. That requires a reasonable supply of protein, methods of purification, success in crystallization and then a """"""""standard"""""""" crystal structure determination. Attempts will be made to predict the structure in advance based on possible homologies. """"""""Random"""""""" tests, designs based on the predicted structure and, eventually, designs based on the actual structure may yield compounds that bind to the anticipated hydrophobic interior of p24. These compounds can be initially tested in binding studies (see program D1 on """"""""Learning Drug Design: Inhibition of Uncoating in Animal RNA Viruses"""""""") and crystallographic difference maps. If success is achieved, these compounds will then be tested for inhibiting infectivity and will, in turn, lead to the design of drugs with improved efficacy.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Purdue University
West Lafayette
United States
Zip Code
Ehrlich, L S; Agresta, B E; Gelfand, C A et al. (1994) Spectral analysis and tryptic susceptibility as probes of HIV-1 capsid protein structure. Virology 204:515-25
Agrawal, D K; Johnson, J E (1992) Sequence and analysis of the capsid protein of Nudaurelia capensis omega virus, an insect virus with T = 4 icosahedral symmetry. Virology 190:806-14
Giranda, V L; Heinz, B A; Oliveira, M A et al. (1992) Acid-induced structural changes in human rhinovirus 14: possible role in uncoating. Proc Natl Acad Sci U S A 89:10213-7
Prongay, A J; Smith, T J; Rossmann, M G et al. (1990) Preparation and crystallization of a human immunodeficiency virus p24-Fab complex. Proc Natl Acad Sci U S A 87:9980-4