Modeling and forecasting of at home activity in older adults using passive sensor technology.

Life expectancy in the UK has increased since the 19th century. As of 2019, there are just under 12 million people in the UK aged 65 or over, with close to a quarter living by themselves. Thus, many families and carers are looking for new ways to improve the health and care of older people.

Applying graph theory to protein structures: an Atlas of coiled coils.

Motivation: To understand protein structure, folding and function fully and to design proteins de novo reliably, we must learn from natural protein structures that have been characterized experimentally. The number of protein structures available is large and growing exponentially, which makes this task challenging. Indeed, computational resources are becoming increasingly important for classifying and analyzing this resource.

'Something in the way she moves': The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI).

Protein disulfide isomerase (PDI) has diverse functions in the endoplasmic reticulum as catalyst of redox transfer, disulfide isomerization and oxidative protein folding, as molecular chaperone and in multi-subunit complexes. It interacts with an extraordinarily wide range of substrate and partner proteins, but there is only limited structural information on these interactions. Extensive evidence on the flexibility of PDI in solution is not matched by any detailed picture of the scope of its motion.

Membrane-spanning α-helical barrels as tractable protein-design targets.

The rational () design of membrane-spanning proteins lags behind that for water-soluble globular proteins. This is due to gaps in our knowledge of membrane-protein structure, and experimental difficulties in studying such proteins compared to water-soluble counterparts. One limiting factor is the small number of experimentally determined three-dimensional structures for transmembrane proteins.

ISAMBARD: an open-source computational environment for biomolecular analysis, modelling and design.

Motivation: The rational design of biomolecules is becoming a reality. However, further computational tools are needed to facilitate and accelerate this, and to make it accessible to more users.

Results: Here we introduce ISAMBARD, a tool for structural analysis, model building and rational design of biomolecules.

Engineering protein stability with atomic precision in a monomeric miniprotein.

Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding temperature (T) of 39 °C.

De novo protein design: how do we expand into the universe of possible protein structures?

Protein scientists are paving the way to a new phase in protein design and engineering. Approaches and methods are being developed that could allow the design of proteins beyond the confines of natural protein structures. This possibility of designing entirely new proteins opens new questions: What do we build? How do we build into protein-structure space where there are few, if any, natural structures to guide us? To what uses can the resulting proteins be put? And, what, if anything, does this pursuit tell us about how natural proteins fold, function and evolve? We describe the origins of this emerging area of fully de novo protein design, how it could be developed, where it might lead, and what challenges lie ahead.

Characterization of folding cores in the cyclophilin A-cyclosporin A complex.

Determining the folding core of a protein yields information about its folding process and dynamics. The experimental procedures for identifying the amino acids that make up the folding core include hydrogen-deuterium exchange and Φ-value analysis and can be expensive and time consuming. Because of this, there is a desire to improve upon existing methods for determining protein folding cores theoretically.

Does deamidation cause protein unfolding? A top-down tandem mass spectrometry study.

Deamidation is a nonenzymatic post-translational modification of asparagine to aspartic acid or glutamine to glutamic acid, converting an uncharged amino acid to a negatively charged residue. It is plausible that deamidation of asparagine and glutamine residues would result in disruption of a proteins' hydrogen bonding network and thus lead to protein unfolding. To test this hypothesis Calmodulin and B2M were deamidated and analyzed using tandem mass spectrometry on a Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS).