This proposal is to request support for a pair of concurrent 2008 Keystone meetings entitled """"""""Frontiers of Structural Biology"""""""" (organized by Wolfgang P. Baumeister, Elena Conti and Gerhard Wagner), and """"""""Structural Genomics and Its Applications to Chemistry, Biology and Medicine"""""""" (organized by Ian A. Wilson, Janet M. Thornton and Kurt W?thrich), which will be held in Steamboat Springs, Colorado from January 6 - 11, 2008. Single proteins can catalyze biochemical reactions, but higher cellular functions depend on carefully orchestrated protein interactions. This poses the challenge for structural biology to develop strategies for studying large complexes and supramolecular assemblages ('functional modules'). Moreover, to understand function we must study the dynamics of macromolecular systems on different time and length scales, or at least we must try to obtain snapshots of key intermediate states. These trends are clearly reflected by the provisional program for Frontiers in Structural Biology. Structural biology will increasingly rely on hybrid approaches combining high-resolution structures of molecular components with lower resolution structures of larger assemblages - from complexes to organelles and even whole cells. With regard to the meeting on Structural Genomics and Its Applications to Chemistry, Biology and Medicine, structural genomics has already significantly advanced high throughput (HT) technologies, including automation and robotics, for cloning, expression, purification and determination of protein structures by crystallography and NMR. These methodologies are now being applied to the field of proteomics to accelerate our understanding of the ever expanding protein universe (fold and function) as a result of the explosion in gene sequencing and to tackle challenging targets, such as membrane proteins, macromolecular complexes and eukaryotic targets. This meeting will focus on current approaches in structural genomics and on how structural genomics tools can be applied to topical problems in structural, molecular, cell and chemical biology not only within large consortia, but also for single investigator laboratories and smaller scale projects. In this way, the enormous complexity presented by even single proteomes -- such as human, mouse, as well as human pathogens -- can be tackled so as too significantly impact chemical, biological and biomedical research. These two joint Keystone Symposia will focus on recent developments in structural biology and their impact on the understanding of key biological problems, as well as the most topical key issues in structural genomics. The pairing of these meetings will promote a molecular level understanding of normal biological function and aberrant function in disease, advance the development of new therapeutic approaches for treating human diseases, and help advance application of the latest structural biology technologies in the wider structural biology community. These meetings will provide a forum to accelerate the progress of structural biology programs and enhance their overall impact on biology, medicine, and chemistry. ? ? ?