5FNH: Native State Mass Spectrometry, Surface Plasmon Resonance And X-ray Crystallography Correlate Strongly As A Fragment Screening Combination

Citation:
Abstract
Fragment-based drug discovery (FBDD) is contingent on the development of analytical methods to identify weak protein-fragment noncovalent interactions. Herein we have combined an underutilized fragment screening method, native state mass spectrometry, together with two proven and popular fragment screening methods, surface plasmon resonance and X-ray crystallography, in a fragment screening campaign against human carbonic anhydrase II (CA II). In an initial fragment screen against a 720-member fragment library (the "CSIRO Fragment Library") seven CA II binding fragments, including a selection of nonclassical CA II binding chemotypes, were identified. A further 70 compounds that comprised the initial hit chemotypes were subsequently sourced from the full CSIRO compound collection and screened. The fragment results were extremely well correlated across the three methods. Our findings demonstrate that there is a tremendous opportunity to apply native state mass spectrometry as a complementary fragment screening method to accelerate drug discovery.
PDB ID: 5FNHDownload
MMDB ID: 137045
PDB Deposition Date: 2015/11/15
Updated in MMDB: 2016/03
Experimental Method:
x-ray diffraction
Resolution: 1.66  Å
Source Organism:
Similar Structures:
Biological Unit for 5FNH: monomeric; determined by author and by software (PISA)
Molecular Components in 5FNH
Label Count Molecule
Protein (1 molecule)
1
Carbonic Anhydrase 2(Gene symbol: CA2)
Molecule annotation
Chemicals (6 molecules)
1
1
2
2
3
1
4
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.