Proteins and their interacting partners: an introduction to protein–ligand binding site prediction methods

Elucidating the biological and biochemical roles of proteins, and subsequently determining their interacting partners, can be difficult and time consuming using in vitro and/or in vivo methods, and consequently the majority of newly sequenced proteins will have unknown structures and functions. However, in silico methods for predicting protein–ligand binding sites and protein biochemical functions offer an alternative practical solution. The characterisation of protein–ligand binding sites is essential for investigating new functional roles, which can impact the major biological research spheres of health, food, and energy security. In this review we discuss the role in silico methods play in 3D modelling of protein–ligand binding sites, along with their role in predicting biochemical functionality. In addition, we describe in detail some of the key alternative in silico prediction approaches that are available, as well as discussing the Critical Assessment of Techniques for Protein Structure Prediction (CASP) and the Continuous Automated Model EvaluatiOn (CAMEO) projects, and their impact on developments in the field. Furthermore, we discuss the importance of protein function prediction methods for tackling 21st century problems.

Can site and landscape-scale environmental attributes buffer bird populations against weather events?

Projected impacts of climate change on the populations and distributions of species pose a challenge for conservationists. In response, a number of adaptation strategies to enable species to persist in a changing climate have been proposed. Management to maximise the quality of habitat at existing sites may reduce the magnitude or frequency of climate-driven population declines. In addition large-scale management of landscapes could potentially improve the resilience of populations by facilitating inter-population movements. A reduction in the obstacles to species’ range expansion, may also allow species to track changing conditions better through shifts to new locations, either regionally or locally. However, despite a strong theoretical base, there is limited empirical evidence to support these management interventions. This makes it difficult for conservationists to decide on the most appropriate strategy for different circumstances. Here extensive data from long-term monitoring of woodland birds at individual sites are used to examine the two-way interactions between habitat and both weather and population count in the previous year. This tests the extent to which site-scale and landscape-scale habitat attributes may buffer populations against variation in winter weather (a key driver of woodland bird population size) and facilitate subsequent population growth. Our results provide some support for the prediction that landscape-scale attributes (patch isolation and area of woodland habitat) may influence the ability of some woodland bird species to withstand weather-mediated population declines. These effects were most apparent among generalist woodland species. There was also evidence that several, primarily specialist, woodland species are more likely to increase following population decline where there is more woodland at both site and landscape scales. These results provide empirical support for the concept that landscape-scale conservation efforts may make the populations of some woodland bird species more resilient to climate change. However in isolation, management is unlikely to provide a universal benefit to all species.

Frontline safety: understanding the workplace as a site of regulatory engagement

The concept of frontline safety encapsulates an approach to occupational health and safety that emphasizes the 'other side of the regulatory relationship' – the ways in which safety culture, individual responsibility, organizational citizenship, trust, and compliance are interpreted and experienced at the local level. By exploring theoretical tensions over the most appropriate way of conceptualizing and framing frontline regulatory engagement, we can better identify the ways in which conceptions of individuals (as rational, responsible, economic actors) are constructed and maintained through workplace interactions and decision-making, as part of the fulfilment of the ideological and constitutive needs of neoliberal labor markets.

Proposal for a unified nomenclature for target site mutations associated with resistance to fungicides

Evolved resistance to fungicides is a major problem limiting our ability to control agricultural, medical and veterinary pathogens and is frequently associated with substitutions in the amino acid sequence of the target protein. The convention for describing amino-acid substitutions is to cite the wild type amino acid, the codon number and the new amino acid, using the one letter amino acid code. It has frequently been observed that orthologous amino acid mutations have been selected in different species by fungicides from the same mode of action class, but the amino acids have different numbers. These differences in numbering arise from the different lengths of the proteins in each species. The purpose of the current paper is to propose a system for unifying the labelling of amino acids in fungicide target proteins. To do this we have produced alignments between fungicide target proteins of relevant species fitted to a well-studied “archetype” species. Orthologous amino acids in all species are then assigned numerical “labels” based on the position of the amino acid in the archetype protein.