In silico structural modeling of multiple epigenetic marks on DNA.

Availability And Implementation: The code together with examples and tutorials are available from http://www.cs.ox.

Co-evolution techniques are reshaping the way we do structural bioinformatics.

Co-evolution techniques were originally conceived to assist in protein structure prediction by inferring pairs of residues that share spatial proximity. However, the functional relationships that can be extrapolated from co-evolution have also proven to be useful in a wide array of structural bioinformatics applications. These techniques are a powerful way to extract structural and functional information in a sequence-rich world.

Study protocol: families and childhood transitions study (FACTS) - a longitudinal investigation of the role of the family environment in brain development and risk for mental health disorders in community based children.

Background: Extant research has demonstrated that parenting behaviour can be a significant contributor to the development of brain structure and mental health during adolescence. Nonetheless, there is limited research examining these relationships during late childhood, and particularly in the critical period of brain development occurring between 8 and 10 years of age. The effects of the family environment on the brain during late childhood may have significant implications for later functioning, and particularly mental health.

Variable Regions of Antibodies and T-Cell Receptors May Not Be Sufficient in Molecular Simulations Investigating Binding.

Antibodies and T-cell receptors are important proteins of the immune system that share similar structures. Both contain variable and constant regions. Insight into the dynamics of their binding can be provided by computational simulations.

Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania.

The indigenous populations of the South Pacific experience a high burden of rheumatic heart disease (RHD). Here we report a genome-wide association study (GWAS) of RHD susceptibility in 2,852 individuals recruited in eight Oceanian countries. Stratifying by ancestry, we analysed genotyped and imputed variants in Melanesians (607 cases and 1,229 controls) before follow-up of suggestive loci in three further ancestral groups: Polynesians, South Asians and Mixed or other populations (totalling 399 cases and 617 controls).

Differential Targeting of Hsp70 Heat Shock Proteins HSPA6 and HSPA1A with Components of a Protein Disaggregation/Refolding Machine in Differentiated Human Neuronal Cells following Thermal Stress.

Heat shock proteins (Hsps) co-operate in multi-protein machines that counter protein misfolding and aggregation and involve DNAJ (Hsp40), HSPA (Hsp70), and HSPH (Hsp105α). The HSPA family is a multigene family composed of inducible and constitutively expressed members. Inducible HSPA6 (Hsp70B') is found in the human genome but not in the genomes of mouse and rat.

Sphinx: merging knowledge-based and ab initio approaches to improve protein loop prediction.

Motivation: Loops are often vital for protein function, however, their irregular structures make them difficult to model accurately. Current loop modelling algorithms can mostly be divided into two categories: knowledge-based, where databases of fragments are searched to find suitable conformations and ab initio, where conformations are generated computationally. Existing knowledge-based methods only use fragments that are the same length as the target, even though loops of slightly different lengths may adopt similar conformations.

A multi-crystal method for extracting obscured crystallographic states from conventionally uninterpretable electron density.

In macromolecular crystallography, the rigorous detection of changed states (for example, ligand binding) is difficult unless signal is strong. Ambiguous ('weak' or 'noisy') density is experimentally common, since molecular states are generally only fractionally present in the crystal. Existing methodologies focus on generating maximally accurate maps whereby minor states become discernible; in practice, such map interpretation is disappointingly subjective, time-consuming and methodologically unsound.

Cross-linking mass spectrometry identifies new interfaces of Augmin required to localise the γ-tubulin ring complex to the mitotic spindle.

The hetero-octameric protein complex, Augmin, recruits γ-Tubulin ring complex (γ-TuRC) to pre-existing microtubules (MTs) to generate branched MTs during mitosis, facilitating robust spindle assembly. However, despite a recent partial reconstitution of the human Augmin complex , the molecular basis of this recruitment remains unclear. Here, we used immuno-affinity purification of Augmin from and cross-linking/mass spectrometry to identify distance restraints between residues within the eight Augmin subunits in the absence of any other structural information.

Partial-occupancy binders identified by the Pan-Dataset Density Analysis method offer new chemical opportunities and reveal cryptic binding sites.

Crystallographic fragment screening uses low molecular weight compounds to probe the protein surface and although individual protein-fragment interactions are high quality, fragments commonly bind at low occupancy, historically making identification difficult. However, our new Pan-Dataset Density Analysis method readily identifies binders missed by conventional analysis: for fragment screening data of lysine-specific demethylase 4D (KDM4D), the hit rate increased from 0.9% to 10.

The H3 loop of antibodies shows unique structural characteristics.

The H3 loop in the Complementarity Determining Region of antibodies plays a key role in their ability to bind the diverse space of potential antigens. It is also exceptionally difficult to model computationally causing a significant hurdle for in silico development of antibody biotherapeutics. In this article, we show that most H3s have unique structural characteristics which may explain why they are so challenging to model.

WONKA and OOMMPPAA: analysis of protein-ligand interaction data to direct structure-based drug design.

In this work, two freely available web-based interactive computational tools that facilitate the analysis and interpretation of protein-ligand interaction data are described. Firstly, WONKA, which assists in uncovering interesting and unusual features (for example residue motions) within ensembles of protein-ligand structures and enables the facile sharing of observations between scientists. Secondly, OOMMPPAA, which incorporates protein-ligand activity data with protein-ligand structural data using three-dimensional matched molecular pairs.

Antibody H3 Structure Prediction.

Antibodies are proteins of the immune system that are able to bind to a huge variety of different substances, making them attractive candidates for therapeutic applications. Antibody structures have the potential to be useful during drug development, allowing the implementation of rational design procedures. The most challenging part of the antibody structure to experimentally determine or model is the H3 loop, which in addition is often the most important region in an antibody's binding site.

Comparing co-evolution methods and their application to template-free protein structure prediction.

Motivation: Co-evolution methods have been used as contact predictors to identify pairs of residues that share spatial proximity. Such contact predictors have been compared in terms of the precision of their predictions, but there is no study that compares their usefulness to model generation.

Results: We compared eight different co-evolution methods for a set of ∼3500 proteins and found that metaPSICOV stage 2 produces, on average, the most precise predictions.

"Nutraceuticals" in relation to human skeletal muscle and exercise.

Skeletal muscles have a fundamental role in locomotion and whole body metabolism, with muscle mass and quality being linked to improved health and even lifespan. Optimizing nutrition in combination with exercise is considered an established, effective ergogenic practice for athletic performance. Importantly, exercise and nutritional approaches also remain arguably the most effective countermeasure for muscle dysfunction associated with aging and numerous clinical conditions, e.

Components of a mammalian protein disaggregation/refolding machine are targeted to nuclear speckles following thermal stress in differentiated human neuronal cells.

Heat shock proteins (Hsps) are a set of highly conserved proteins involved in cellular repair and protective mechanisms. They counter protein misfolding and aggregation that are characteristic features of neurodegenerative diseases. Hsps act co-operatively in disaggregation/refolding machines that assemble at sites of protein misfolding and aggregation.

Computational Tools for Aiding Rational Antibody Design.

Antibodies are a group of proteins responsible for mediating immune reactions in vertebrates. They are able to bind a variety of structural motifs on noxious molecules tagging them for elimination from the organism. As a result of their versatile binding properties, antibodies are currently one of the most important classes of biopharmaceuticals.

Arteriovenous access ischemic steal (AVAIS) in haemodialysis: a consensus from the Charing Cross Vascular Access Masterclass 2016.

Arteriovenous access ischaemic steal (AVAIS) is a serious and not infrequent complication of vascular access. Pathophysiology is key to diagnosis, investigation and management. Ischaemia distal to an AV access is due to multiple factors.