Mathematical modeling of protein complexes (Q1793985)

Proteins represent one of the most important types of macromolecules in the living world, performing a multitude of functions. Protein molecules are characterised by their so-called conformation which, in turn, depends on the sequence of amino acids that form them; the resulting active binding sites are responsible for the formation of protein complexes. Since, however, the exact conformation of a protein may not be known, a crucial challenge in proteomics is the experimental determination of interactions and affinities between proteins which then also determine the stability of the resulting complexes. Similar complications arise when the native conformation, while known, is violated by various stresses, potentially resulting in pathological states. In modern proteomics, protein interactions are typically studied via so-called conformational search algorithms. When the structure of a given protein is known, intermolecular interactions may be reduced to the question of whether the geometry of the corresponding molecular surfaces is complementary, allowing for docking. Here, the authors argue that various factors which may significantly affect molecular docking -- such as the conformational mobility of the target protein -- are not accounted for by standard search algorithms. Further, they reason that the consideration of such factors through common modelling approaches requires an overly high computational effort, resulting in data that is difficult to interpret from a practical point of view. In an attempt to remedy these deficiencies, the authors present in their monograph a number of mathematical models which, in their algorithmic implementation, allow them to consider different, if rather specific, physiological scenarios; in fact, following an introductory Chapter~1 which summarises the use of experimental techniques in proteomics, each chapter of the monograph encompasses one such scenario. Chapter~2 is concerned with the mathematics of complex formation; in Chapter~3, temperature effects are considered; Chapter~4 addresses the impact of salinity; in Chapter~5, the identification of active sites is discussed; Chapter~6 is concerned with phosphorylation; in Chapter~7, point mutations are considered; finally, in Chapter~8, therapeutic peptides are studied. Throughout, the biophysical foundations of these various scenarios are elaborated on in some detail, and related to numerical results obtained from the authors' algorithms. Naturally, the focus of the monograph is on the description of the latter, with \textsc{Matlab} scripts at the end of each chapter allowing for them to be reproduced and adapted by the interested reader. Given the wide range of biophysical and medical applications covered -- albeit in somewhat condensed form -- and the generalisable nature of the algorithms proposed by the authors, it is to be expected that the monograph will be of interest to researchers in the field of applied proteomics who possess an aptitude for mathematical modelling and numerical simulation.