With the addition of Dr Dan Rigden (email@example.com) to the supervisory staff, a range of services across protein sequence and structure bioinformatics are now available to help you predict, understand and redesign protein activities. They cover protein modelling of all kinds and the use of such models for applications, from biomedical eg structure-based SNP interpretation, to biotechnological eg genome mining, protein design.
Genome mining for commercially valuable enzyme activities
In collaboration with Dr Andrew Carnell (Chemistry) and Biome Technologies, naturally occurring enzymes suitable to help convert waste material-derived compounds to bioplastic precursors were sought. This entailed genome mining and structure-based screening of proteins for appropriate catalytic site architecture. Candidate proteins are being expressed in the company GeneMill.
Function annotation of a bacterial effector protein
Pathogenic bacteria often manipulate host cells using effector proteins, many of which are recalcitrant to function annotation by automated pipelines. Distant homology detection and structure modelling predicted that Legionella pneumophila effector Lpg0393 was a guanine-nucleotide exchange factor that interfered with host cell signalling. This was confirmed in collaboration with Prof Oh, KAIST, Korea (Sohn et al., 2015).
Ab initio structure prediction of a cryptic protein interaction domain
In collaboration with Profs Clague and Urbe (ITM) ab initio structure modelling was done of a newly discovered protein interaction domain in KCTD6, an adapter protein in ubiquitin-based signalling. This revealed a striking similarity to a domain found in a protein binding to the ubiquitin ligase NEDD4, and could be used to interpret the experimental data (Heride et al., 2016).
Modelling and function prediction of a novel rodent urinary protein
In collaboration with Profs Beyon and Hurst (IIB) and the Centre for Proteome Research, homology modelling of a novel protein glareosin was done. This confirmed the existence of a central ligand binding cavity – required for the biological function of most such proteins – but revealed a different size and shape to close relatives, hinting at distinct binding specificity (Loxley et al., 2017).
Protein redesign for commercially valuable enzyme activities
Naturally-occurring molecules offer inspiration for improved UV-absorbing compounds suitable for formulation in sunscreens. In collaboration with Dr Andrew Carnell (Chemistry) and Unilever, sequence- and structure-based analyses were used to reshape the natural catalytic site of a bacterial protein, aiming for novel substrate specificity. Candidate sequences are being expressed in the the company GeneMill.