Support is requested for a Keystone Symposia meeting entitled Hybrid Methods in Structural Biology, organized by Jens Meiler, Patrick Cramer and Ron A. Milligan. The meeting will be held in Tahoe City, California from March 4-8, 2015. As we study the structure and dynamics of more and more complex systems to better understand their biological function, each individual technology in the structural biology toolbox approaches its limitations. These limitations include size of the system, timeline of motions, spatial and/or temporal resolution, and ensemble averaging. Further, each individual method perturbs the system in a different way to enable or facilitate its analysis. This includes for example the introduction of spin labels to perform EPR experiments, the reconstitution of membrane proteins in micelles for NMR spectroscopy, the introduction of entire domains to stabilize proteins in certain conformations for crystallization, or a simplified force field in computation. As systems become more challenging, the perturbations tend to get more drastic, complicating the interpretation of results. Only at the intersection of several techniques it becomes possible to distinguish information that is biologically relevant from perturbations introduced by any individual approach. Moving forward, hybrid methods and integrated methods in structural biology play a key role in studying complex systems verifying each other's results. The objective of this Keystone Symposia meeting is two-fold: 1) To discuss novel and potentially disruptive technologies and/or combinations thereof to be added to the hybrid methods toolbox; and 2) To illustrate and discuss application of hybrid methods to important biological systems. These objectives will be achieved not only by a line-up of exceptional oral presentations, but also by prominently placed poster sessions, discussions in panel format, and tutorial sessions introducing new software algorithms.
Drug discovery generally benefits from a mechanistic molecular understanding of normal and disease processes. Hybrid methods and integrated methods in structural biology play a key role in studying complex systems verifying each other's results. The Keystone Symposia meeting on Hybrid Methods in Structural Biology will highlight the strengths and limitations of the current hybrid approaches to structural characterization, and identify new promising advances in experimental methods for collecting the data and computational methods for converting the data to models.
