MOLECULAR STRUCTURE OF ANIMAL VIRUSES AND CELLS BY COMPUTATIONAL ANALYSIS

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Complex macromolecular processes and the organization of normal, infected and transformed cells are modeled using viral systems. Computers are used to study nucleic acid and protein sequences that embody the information needed by these systems to function. Gene and protein sequences of HIV, and related viruses are analyzed by computer methods to find relationships among them and to other known and hypothetical proteins. Predicted secondary structures of their RNAs vary in correlation with pathological and sequence differences. Foot-and-mouth viruses and adenoviruses are studied with a goal to understanding early events in virus replication wherein the cell's metabolism is subverted to viral functions, and late events during which assembly and morphogenesis occurs. Early viral proteins, whose existence was known from biochemical studies, have been analyzed by comparing their sequences to cellular proteins of known function. Computer analysis of proteins and nucleic acids are developed and implemented in conjunction with techniques of biochemistry, virology, and electron microscopy on sequences of picornaviruses, adenoviruses, human immunodeficiency viruses. Graphic representations revealing homology, and reverse complementarity are coupled with numerical methods to aid the prediction of secondary structure, splicing, promoters, and recombination in nucleic acid molecules. Computer programs are developed locally and elsewhere for application on Cray XMP, VAX and graphic workstations to perform sequence analysis and structure predictions. Methods to assess the significance of predictions use Monte Carlo simulations, evolutionary comparisons and biochemical data. Roles for genes and proteins are deduced by comparison with databases of sequences of known function and structure.