High Resolution Energy Functions for Protein Structure Determination and Prediction

We have recently demonstrated that the intimate relationship between energy and structure can be used to refine structures and energy functions in a self-consistent manner. In the present project this principle of self-consistent refinement is used to correct inconsistencies in experimental structures where the refined structures immediately yield potential functions of higher accuracy. In structural biology energy functions and scoring schemes play a fundamental role. Aside from structure refinement the energy functions derived in this project will be employed in the calculation of structures from chemical shift data obtained from NMR experiments, in the prediction and modeling of protein structures, and in the discovery and analysis of protein function. The chief goal of this project is the development of precise and accurate energy functions for the pairwise atomic interactions in proteins and their application in protein structure refinement. To obtain these energy functions we exploit the intimate relationship between structure and energy. Detailed structural information on the various pairwise atomic interactions is encoded in the respective radial distribution functions which may be compiled from the set of known protein structures. The associated potentials of mean force (energy) are then obtained by a straightforward transformation of the radial distribution functions (structure).