Normal Mode Flexible Fitting of High-Resolution Structures of Biological Molecules Toward SAXS Data

Abstract

We present a method to reconstruct a three-dimensional protein structure from an atomic pair distribution function derived from the scattering intensity profile from SAXS data by flexibly fitting known x-ray structures. This method uses a linear combination of low-frequency normal modes from an elastic network description of the molecule in an iterative manner to deform the structure to conform optimally to the target pair distribution function derived from SAXS data. For computational efficiency, the protein and water molecules included in the protein first hydration shell are coarse-grained. In this paper, we demonstrate the validity of our coarse- graining approach to study SAXS data. Illustrative results of our flexible fitting studies on simulated SAXS data from five different proteins are presented.