MOLECULAR STRUCTURE OF ANIMAL VIRUSES AND CELLS BY COMPUTATIONAL ANALYSIS

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Viral systems are used to model the complex macromolecular processes and organization of normal, infected and transformed cells. Computers are used to study the nucleic acid and protein sequences that embody the information necessary for these systems to function. Picornaviruses cause diseases typified by polio, colds, hepatitis, and foot-and-mouth diseases. Gene and protein sequences of these viruses are comparatively studied for relationships among them and to other known and hypothetical proteins. Secondary structures of the RNAs are found to vary in correlation with pathological and sequence differences. 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 analyses of proteins and nucleic acids have been 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.