This research will encompass two distinct projects in the area of biomolecular structure-function studies: 1) Construction of selected mutants of E. coli dihydrofolate reductase (DHFR); by x-ray crystallography observe the structural perturbations effected by these mutations; and characterize the catalytic properties of the mutant enzymes by steady-state and pre-steady-state kinetic methods, focusing on individual elementary steps in the pathway. The goal of this project is to answer various fundamental questions about the stereochemical mechanism that arise upon examination of crystal structures of E. coli DHFR and three other species of DHFR previously determined in this laboratory. 2) X-ray crystallographic structure determination of several lymphokines, including especially interleukin-2 and interferon- alpha. The lymphokines are a class of protein molecules that act as intercellular signals of the immune system. It is hoped to identify and examine the chemical geometry of the sites on these molecules that interact with their receptors and thereby elicit biological activity.