JOHNS HOPKINS UNIV BALTIMORE MD DEPT OF MOLECULAR BIOLOGY AND GENETICS
Our fundamental goal is to develop methods for de novo protein design, and we are proceeding by treating the problem of protein design as an inverted version of the protein folding problem. In the protein folding problem, one is given an amino acid sequence and must predict how this folds in three dimensions. Protein design can be approached in quite a different way - one can begin by choosing a folded arrangement of the polypeptide backbone and then try to pick an amino acid sequence that will stabilize this structure. Inversion eliminates the problem of predicting long-range interactions, since residues which will interact in the final tertiary or quaternary structure already are close in space when they are added to the prefolded backbone. One should be able to pick residues which will have favorable interactions with their neighbors. We are developing a program, called PDB PROTEUS, for computed-aided protein design. Our program uses simple geometric aspects of protein structure and frequently uses local coordinate systems so that the geometric relationships are easier to visualize Pabo and Suchanek, 1986. There are many advantages to using a computer program A program can easily check millions of possible sequences and conformations. Using a program also makes it easy to try several variations of a particular search strategy or to apply the same strategy to many different proteins. Keywords Computer aided design Molecular biology Computer programs Synthesis chemistry Computer simulation.