Knowledge of molecular structure is essential for our understanding of biological systems. X-ray crystallography is widely used to determine the 3-dimensional structure of proteins, nucleic acids, and large nucleoprotein complexes. It exploits the propensity of X-rays to be scattered by the electron clouds around atoms. The "electron density" can be reconstructed from diffraction patterns obtained from single crystals of the target molecule. An atomic model is then built into the electron density, which in turn is refined against the data, eventually resulting in an accurate molecular structure in which the coordinates of every atom with respect to every other atom is known precisely.

While X-ray crystallography can provide details on structural information for mechanistic analyses, it is, however, restricted to describing low energy conformations of macromolecules within crystal lattices. Small-angle X-ray scattering (SAXS) offers complementary information about macromolecular folding, unfolding, aggregation, extended conformations, flexibly linked domains, shape, conformation, and assembly state in solution, at a lower resolution range. Combining X-ray crystallography with SAXS, it can allow multi-scale modeling to create complete and accurate atomic resolution structural images of macromolecules for modeling allosteric mechanisms, supramolecular complexes, and dynamic molecular machines. The figure below shows a typical SAXS flow.

Monte Carlo simulations are proving quite useful for modeling of SAXS data, and are expected to allow continued advances in SAXS data interpretation tools. Various groups have succeeded in developing computational method that can provide theoretical scattering patterns based on a model, which is adjusted until the predicated scattering pattern matches the measured pattern. This process, as with Monte Carlo simulations, is computationally intensive and therefore requires high-performance computing support.