The control of biological processes rests at the level of individual proteins and their
interactions with other proteins, small molecules, nucleic acids, and environmental stimuli. A thorough understanding
of the activity of a molecular system requires knowledge of the three-dimensional structure of the macromolecules
involved in the process. The Biosciences Division is pioneering cutting-edge technologies to determine the
three-dimensional structures of macromolecules and to carry out comprehensive functional characterization of
biomolecules. Study of the three-dimensional structures of macromolecules is referred to as structural biology and the
high-throughput analysis of the structures of molecules across an entire genome is referred to as structural genomics.
The comprehensive analysis of molecular function at a genome-wide level is called functional genomics.
Recent developments in genome-scale DNA sequencing, high-throughput analytical tools, and computing technology have made feasible the genome-wide analysis of biomolecular function. Construction of complete functional maps of cellular behavior now appears to be achievable. Functional analysis of the thousands of proteins and other macromolecules needed for a comprehensive analysis of even the simplest prokaryote is a significant technological challenge that will require substantial enhancement of currently available experimental and computational capabilities. The amount of data needed to functionally characterize an organism greatly exceeds that required to sequence its genome. Furthermore, unlike genome sequencing, functional analysis requires multiple high-throughput experimental technologies and novel computational approaches.
Nevertheless, the comprehensive characterization of biomolecular function has huge potential payoffs. It will provide the basis for developing entirely new strategies for modulating cellular activities and engineering novel cellular capabilities. These opportunities can provide the basis for novel solutions to problems associated with the DOE science mission, and they will be particularly important for advancing the DOE national security mission through the study of organisms used as biowarfare agents. More broadly, the resulting capabilities will enable major benefits for environmental management, human health, and general economic productivity.
