X-ray Solution Scattering Combined with Computation Characterizing Protein Folds and Multiple Conformational States: Computation and Application

Abstract

Small angle X-ray scattering (SAXS) is an increasingly powerful technique to characterize the structure of biomolecules in solution. We present a computational method for accurately and efficiently computing the solution scattering curve from a protein with dynamical fluctuations. The method is built upon a coarse-grained (CG) representation of the protein. This CG approach takes advantage of the low-resolution character of solution scattering. It allows rapid determination of the scattering pattern from conformations extracted from CG simulations to obtain scattering characterization of the protein conformational landscapes. Important elements incorporated in the method include an effective residue-based structure factor for each amino acid, an explicit treatment of the hydration layer at the surface of the protein, and an ensemble average of scattering from all accessible conformations to account for macromolecular flexibility. The CG model is calibrated and illustrated to accurately reproduce the experimental scattering curve of Hen egg white lysozyme. We then illustrate the computational method by calculating the solution scattering pattern of several representative protein folds and multiple conformational states. The results suggest that solution scattering data, when combined with a reliable computational method, have great potential for a better structural description of multi-domain complexes in different functional states, and formore » recognizing structural folds when sequence similarity to a protein of known structure is low. Possible applications of the method are discussed.« less