Preface

Amino acids, peptides and proteins is a series of specialist periodical reports that provides a comprehensive overview of contemporary research in protein and peptide science – a continuous tradition started in 1969. The series covers diverse developments in the chemistry, biology and application of amino acids, peptides and proteins striving to avoid the bias of topical popularity. In most recent volumes the series included contributions that are not necessarily specific to protein science, but are complementary to help advance the current understanding of this research area. Established and emerging measurement approaches and techniques are reviewed in the light of additional insights gained into the elucidation of protein structure and function. This focus also reflects the increasingly interdisciplinary nature of modern research and emphasises the need for developing innovative measurements. This volume continues this trajectory bringing new and established science together. This book series reviewes literature predominantly published over the last few years, with each chapter outlining underpinning concepts and terminology, which may have been introduced earlier but remain valid to date.

This 44th volume of the series opens with a chapter on the enzymatic halogenation of organic compounds (Dachwitz et al.) as opposed to chemical halogenation, which remains a challenging endeavour. The use of halogenases is an effective alternative to purely chemical methods. These enzymes can hologenate different molecular substrates in a regioselective manner and at target sites including electronically disfavoured positions. The report details the advantages and limitations of such biocatalysts including the narrow choice of substrates, the need for tailor-made enzymes, which is met by directed evolution approaches, and the progress towards providing a variety of biocatalysts. The strategy for the diversification of biochemical tools is echoed in the following chapter (Rich et al.), which discusses non-canonical amino acids as bioactive molecules, molecular scaffolds and building blocks. Contemporary approaches are reviewed for the biocatalytic synthesis of non-canonical amino acids highlighting their use for protein modifications. The chapter provides a helpful clarification of differences between proteinogenic, post-translational and non-canonical amino acids, and compiles a toolbox of non-canonical amino acids with an experimentally proven potential for drug design. Recent successes in the improvement of naturally occuring antimicrobial and anticancer peptides (e.g. lactoferricin, nisin) are discussed. Given examples demonstrate the impact non-canonical amino acids can have on improving the biological properties of these peptides, while allowing for beneficial changes in their conformational properties. The latter is critical for folding-dependent mechanisms, such as those by antimicrobial peptides, as these define the outcome of biological activity. This is the focus of the third chapter (Bodor) which covers the state of the art in the study of intrinsically disordered proteins. The chapter guides through available methodologies to predict intrinsic disorder and inform experimental approaches for the characterisation of disordered proteins with an atomic precision. Links between amino-acid composition and propensity for disorder are assessed in detail. Traditionally, misfolding phenomena are discussed in relation to human neurodegenerative diseases or proteopathies such as Alzheimer's and Parkinson's diseases, the rate of which is increasing with the ageing population in the developed countries. In contrast, this chapter puts a stronger emphasis on the structural composition of the proteins regardless of their origin or implication in diseases. This somewhat fresher take on an old problem helps appreciate the universal nature of intrinsic disorder in proteins. For example, cross-comparisons of disordered residues in viruses and unicellular organisms reveal substantial variations in average fractions of disordered residues, with the highest fractions observed for viral, smallest, proteomes. Several computational disorder predictors are compared emphasising the importance of the continuous development of machine learning algorithms to enable better predictions, the utilisation of which can also be expanded to improved analysis of experimental datasets obtained using high resolution measurements, e.g. X-ray crystallography or X-ray scattering. With the resolution of measurement techniques improving, which allows to elucidate molecular phenomena in greater detail, additional requirements become also more apparent. One of these is the ability to monitor biological processes in real time and in aqueous environments – the feat that is inaccessible to most high resolution methodologies including cryo-electron microscopy and X-ray crystallography. The penultimate chapter addresses this seeming discrepancy between high resolution data and real-time measurements in water using the example of in liquid atomic force microscopy (Hammond et al.). This type of microscopy allows for high resolution imaging of molecular events in response to peptide treatment. As an exemplar, the mechanistic elucidation of antimicrobial mechanisms in phospholipid membranes is described in the chapter. Typically considered as different versions of pore formation, these mechanisms prove to be far more diverse when investigated using atomic force microscopy. At least partly, this is due to the fact that this technique can cover far broader length scales than other high resolution methods and thus is able to reveal processes that would otherwise remain undetected. A complementary consideration to the same issue of precise and specific detection of molecular modifications, processes or mechanisms is the analysis of individual amino-acid modifications in peptides and proteins. This is the topic of the closing chapter, which extends the discussion to high resolution mass-spectrometry methods to detect post-translational modifications of proteins (Steckel et al.). This review assesses the advantages of established mass-spectromentry methods to tackle different challenges including the challenge of identifying over 400 individual and low-abundance post-translational modifications, which are conserved in space and time. Such modifications are considered by many as important biomarkers for personalised medicine. Current problems in overcomming such complex challenges are also detailed. The lack of appropriate internal standards, increased sensitivity and decreased uncertainty of measurement results remain major obstacles towards the reliabe and routine use of these methodologies in clinic. The review concludes the volume with a reiterated message on the necessity of combining computational, bioinformatics capabilities with improved experimental measurements to understand the role of amino acids, peptides and proteins in biology and pathology fully.