Macromolecular structure refinement with chemical accuracy using quantum chemistry tools

Expositor:  Dr. Raúl E. Cachau  –  Frederick National Laboratory for Cancer Research, Frederick, Maryland and Bowie State University, Bowie, Maryland, USA

Fecha:  Martes 06/12/2016 – 11.30 hs.

The Protein Data Bank (PDB) total number of entries at resolution better than 1A now total 722, 355 of which belong to systems with molecular weight greater than 20kD. Our recent analysis of a large set of structures refined at sub-atomic to medium resolutions suggests the chemical accuracy threshold to be ~0.85A resolution and is obtainable in favorable cases only.
The overall quality of the structures rapidly decays at lower resolutions with a fast accumulation of chemical artifacts at resolutions >1.25A. Many errors can be attributed to the qualitative restrains used in the refinement protocols.
I will discuss some of the common artifacts observed, and the results recently obtained using QM/X-ray refinement protocols including the first macromolecular structure solved using a QM restraint without the application of a divide and conquer simplification (Chitinase PDBID:4WKA; PMID: 26143917) using our program QMRx.
Our results suggest chemical accuracy could be extended to the 1.25A -1.5A resolution range in favorable cases, especially when combined with high precision mass spectrometry data. The application of linear scaling full SCF approaches may further help elucidate previously unrecognized long distance couplings within the macromolecular structure as well (PMID: 24573500).