DEAD-END BASED MODELING TOOLS TO EXPLORE THE SEQUENCE SPACE THAT IS COMPATIBLE WITH A GIVEN SCAFFOLD

The dead-end elimination algorithm has proven to be a powerful tool in protein homology modeling since it allows one to determine rapidly th e global minimum-energy conformation (GMEC) of an arbitrarily large co llection of side chains, given fixed backbone coordinates. After intro ducing briefly the necessary background, we focus on logic arguments t hat increase the efficacy of the dead-end elimination process. Second, we present new theoretical considerations on the use of the dead-end elimination method as a tool to identify sequences that are compatible with a given scaffold structure. Third, we initiate a search for prop erties derived from the computed GMEC structure to predict whether a g iven sequence can be well packed in the core of a protein. Three prope rties will be considered: the nonbonded energy, the accessible surface area, and the extent by which the GMEC side-chain conformations devia te from a locally optimal conformation.