Nick Fowler

• PhD
• Research Associate at The University of Sheffield

Protein solubility and stability depend on the co-solutes present. There is little theoretical basis for selection of suitable co-solutes. Some guidance is provided by the Hofmeister series, an empirical ordering of anions according to their effect on solubility and stability; and by osmolytes, which are small organic molecules produced by cells to...

Protein structures calculated using NMR data are less accurate and less well-defined than they could be. Here we use the program ANSURR to show that this deficiency is at least in part due to a lack of hydrogen bond restraints. We describe a protocol to introduce hydrogen bond restraints into the structure calculation of the SH2 domain from SH2B1 i...

Protein structures calculated using NMR data are less accurate and less well defined than they could be. Here we use the program ANSURR to show that this deficiency is at least in part due to a lack of hydrogen bond restraints. We then describe a protocol to introduce hydrogen bond restraints into the structure calculation of the SH2 domain from SH...

AlphaFoldn the recent Critical Assessment of Structure Prediction (CASP) competition, AlphaFold2 performed outstandingly. Its worst predictions were for nuclear magnetic resonance (NMR) structures, which has two alternative explanations: either the NMR structures were poor, implying that Alpha-Fold may be more accurate than NMR, or there is a genui...

In the recent CASP (Critical Assessment of Structure Prediction) competition, AlphaFold2 performed outstandingly. Its worst predictions were for NMR structures, which has two alternative explanations: either the NMR structures were poor, implying that AlphaFold may be more accurate than NMR; or there is a genuine difference between crystal and solu...

The program ANSURR measures the accuracy of NMR structures by comparing rigidity obtained from experimental backbone chemical shifts and from structures. We report on ANSURR analysis of 7,000 PDB NMR ensembles within the Protein Data Bank, which can be found at ansurr.com. The accuracy of NMR structures progressively improved up until 2005, but sin...

We recently described a method, ANSURR, for measuring the accuracy of NMR protein structures. It is based on comparing residue-specific measures of rigidity from backbone chemical shifts via the random coil index, and from structures. Here, we report the use of ANSURR to analyse NMR ensembles within the Protein Data Bank (PDB). NMR structures cover...

We present a method that measures the accuracy of NMR protein structures. It compares random coil index [RCI] against local rigidity predicted by mathematical rigidity theory, calculated from NMR structures [FIRST], using a correlation score (which assesses secondary structure), and an RMSD score (which measures overall rigidity). We test its perfo...

We present a method that measures the accuracy of NMR protein structures. It compares random coil index [RCI] against local rigidity predicted by mathematical rigidity theory, calculated from NMR structures [FIRST], using a correlation score (which assesses secondary structure), and an RMSD score (which measures overall rigidity). We test its perfo...

We present a method, Accuracy of NMR Structures using Random Coil Index and Rigidity (ANSURR), that measures the accuracy of NMR protein structures. It provides a residue-by-residue comparison of two measures of local rigidity: the Random Coil Index [RCI] (a measure of the extent to which backbone chemical shifts adopt random coil values); and loca...

ShK is a 35-residue disulfide-linked polypeptide produced by the sea anemone Stichodactyla helianthus, which blocks the potassium channels Kv1.1 and Kv1.3 with pM affinity. An analogue of ShK has been developed that blocks Kv1.3 > 100 times more potently than Kv1.1, and has completed Phase 1b clinical trials for the treatment of autoimmune diseases...

In this work we present the first computational study on the hectochlorin biosynthesis enzyme HctB, which is a unique three-domain halogenase that activates non-amino acid moieties tethered to an acyl-carrier, and as such may have biotechnological relevance beyond other halogenases. We use a combination of small cluster models and full enzyme struc...

Large-scale characterisation of cysteine modification is enabling study of the physicochemical determinants of reactivity. We find that location of cysteine at the amino terminus of an α-helix, associated with activity in thioredoxins, is under-represented in human protein structures, perhaps indicative of selection against background reactivity. A...

Blue copper proteins, such as azurin, show dramatic changes in Cu2+/Cu+ reduction potential upon mutation over the full physiological range. Hence they have important functions in electron transfer and oxidation chemistry and may have potential in biotechnology. The details of what determines these reduction potential changes upon mutation are stil...

Symmetry breaking phase transitions are often accompanied by the formation of topological defects, like in cosmological theories of the early universe, superfluids, liquid crystals or solid state systems. This scenario is described by the Kibble-Zurek mechanism, which predicts respective scaling laws for the defect density ρ. One such scaling law s...