Simulating, Refining, and Modeling Supramolecular Complexes at Multi-resolution and Multi-length Scales
Jianpeng Ma

A set of new computational methods has been developed for simulating, refining, and modeling supermolecular complexes at multi-resolution and multi-length scales.

On the resolution scale, quantized elastic deformational model (QEDM) was designed to reliably describe large-scale protein motions in the absence of amino-acid sequence and atomic coordinates. QEDM yields an accurate description of protein dynamics over a wide range of resolutions even as low as 30 Å. On the length scale, substructure synthesis method (SSM) was developed to derive the motions of a given structure as a collection of those of an assemblage of substructures. SSM was applied to F-actin, a typical filamentous system in cells. The results demonstrated that SSM is capable of scaling the simulation of atomic motions of molecular complexes to a macroscopic length scale.

The QEDM and SSM methods have been successfully applied to assisting structural refinement against cryo-EM and fibre diffraction data, respectively. The results demonstrated that, under the scheme of harmonic modal analysis, structural refinement for seemingly remote experimental techniques can be unified for systems that involve large-scale conformational flexibility.

In order to improve one’s ability to interpret low- to intermediate-resolution density maps, a series of computational methods have been developed. They are methods like sheetminer and sheettracer that are capable of extracting secondary structural features, and methods that can determinate protein topology merely based on information of secondary structural skeletons.

Methods has also been developed for protein folding assisted by SAXS data which carries hope to significantly improve the effective resolution of SAXS technique. Results have shown that SAXS data carry necessary information that is sufficient to derive overall fold of proteins. Such methods will bridge the gap between cryo-EM and x-ray crystallography, in which the small, soluble, and noncrystalizable proteins can be studied.