Diffraction Methods in Molecular Biology Gordon Research Conference

Gordon Research Conferences, East Greenwich RI

Investigators

Abstract

DESCRIPTION (provided by applicant): Partial support is requested for the Gordon Research Conference (GRC) on "Diffraction Methods in Structural Biology" to be held at Bates College, Lewiston, Maine from 7/18/2010 - 7/23/2010. Knowledge of the three dimensional structures of biological molecules is essential in order to understand their mechanism and modes of interaction, and provides an opportunity to modulate their activity in a way that is beneficial to human health. X-ray crystallography is by far the most powerful technique for the high-resolution structure determination of biological molecules (proteins and nucleic acids and their complexes). Advances in methodology have dramatically extended the range of targets that can now be tackled successfully. Recent highlights include highly complex protein- RNA assemblies such as the 70S bacterial ribosome, very large lipid containing viruses, and complexes involved in transcription. There has also been a very significant increase in the number of intrinsic membrane protein structures determined. These include ABC transporters that mediate resistance to anticancer drugs (P glycoprotein) and most recently the structures of a number of G Protein Coupled Receptors. GPCRs and are involved in many diseases and are the targets of almost 50% of modern medicinal drugs. On a more practical level, advances at synchrotron beam lines have facilitated the rapid collection of the hundreds of datasets required for the "fragment fitting" approach to drug screening adopted by many leading pharmaceutical companies. The continued development of methodology is essential in order to tackle ever more challenging biological systems. This GRC is the main forum in the United States for the presentation and discussion of recent advances in all aspects of diffraction methods, ranging from crystallization to model building and refinement. The 2010 meeting will be chaired by Andrew Leslie (MRC LMB, Cambridge) with Ana Gonzalez (Stanford Synchrotron Radiation Laboratory) as vice chair, and will include presentations from many of the key software and hardware developers in the field. Session topics will include crystallization and data collection, radiation damage, synchrotron developments, complementary techniques (SAXS, electron tomography and spectroscopy), structure solution and refinement, challenging problems (including membrane proteins), oral presentation of selected posters, model building and imaging methods of the future such as free electron lasers and diffractive imaging. PUBLIC HEALTH RELEVANCE: Drugs achieve their therapeutic effects by binding tightly and specifically to a target protein, by virtue of shape complementarily, in a way that interferes with the normal functioning of that protein. The three dimensional shape of proteins can be determined by X-ray diffraction methods from crystals of the protein, providing a route to the rational design of drugs. The 2010 Gordon Research Conference in Diffraction Methods in Structural Biology seeks to advance the techniques used in structure determination by providing a forum for the presentation and discussion of recent developments.