New methods for domain structure determination of proteins from solution scattering data

New approaches for domain structure determination of macromolecules from X-ray solution scattering are presented. An ab initio method for building structural models of proteins from the scattering data implemented in the computer program GASBOR employs simulated annealing to find a chain-like spatial distribution of dummy residues (DR), which fits the experimental scattering pattern up to a resolution of 0.5 nm. This method substantially improves the resolution and reliability of models derived from the scattering data. A modification of GASBOR fitting distance distribution data in real space substantially ( by a factor of 3 to 7) speeds up the calculation of DR models. The DR approach is further extended to reconstruct missing domains in multisubunit proteins and fusion proteins and to find probable configurations of missing loops in crystallographic models. Four computer programs have been written to provide appropriate tools for different situations in which a high or low resolution structural model lacks a loop or domain. These methods permit solution scattering analysis to usefully complement the results obtained by high-resolution methods like X-ray crystallography and nuclear magnetic resonance spectroscopy. The efficiency of the presented approaches is illustrated by their application for structure analysis of several proteins, with known and unknown crystal structure, from experimental scattering data.