Molecular modelling: principles and applications

Andrew Leach0582382106, 9780582382107

Preface to the Second Edition The impetus for this second edition is a desire to include some of the new techniques that have emerged in recent years and also extend the scope of the book to cover certain areas that were under-represented (even neglected) in the first edition. In this second volume there are three topics that fall into the first category (density functional theory, bioinformatics/protein structure analysis and chemoinformatics) and one main area in the second category (modelling of the solid state). In addition, of course, a new edition provides an opportunity to take a critical view of the text and to re-organise and update the material. Thus whilst much remains from the first edition, and this second book follows much the same path through the subject, readers familiar with the first edition will find some changes which I hope they will agree are for the better. As with the first edition we initially consider quantum mechanics, but this is now split into two chapters. Thus Chapter 2 provides an introduction to the ab initio and semi-empirical approaches together with some examples of the uses of quantum mechanics. Chapter 3 covers more advanced aspects of the ab initio approach, density functional theory and the particular problems of the solid state. Molecular mechanics is the subject of Chapter 4 and then in Chapter 5 we consider energy minimisation and other ‘static’ techniques. Chapters 6, 7 and 8 deal with the two main simulation methods (molecular dynamics and Monte Carlo). Chapter 9 is devoted to the conformational analysis of ‘small’ molecules but also includes some topics (e.g. cluster analysis, principal components analysis) that are widely used in informatics. In Chapter 10 the problems of protein structure prediction and protein folding are considered; this chapter also contains an introduction to some of the more widely used methods in bioinformatics. In Chapter 11 we draw upon material from the previous chapters in a discussion of free energy calculations, continuum solvent models, and methods for simulating chemical reactions and defects in solids. Finally, Chapter 12 is concerned with modelling and chemoinformatics techniques for discovering and designing new molecules, including database searching, docking, de novo design, quantitative structure-activity relationships and combinatorial library design. As in the first edition, the inexorable pace of change means that what is currently considered ‘cutting edge’ will soon become routine. The examples are thus chosen primarily because they illuminate the underlying theory rather than because they are the first application of a particular technique or are the most recent available. In a similar vein, it is impossible in a volume such as this to even attempt to cover everything and so there are undoubtedly areas which are under-represented. This is not intended to be a definitive historical account or a review of the current state-of-the-art. Thus, whilst I have tried to include many literature references it is possible that the invention of some technique may appear to be incorrectly attributed or a ‘classic’ application may be missing. A general guiding principle has been to focus on those techniques that are in widespread use rather than those which are the province of one particular research group. Despite these caveats I hope that the coverage is sufficient to provide a solid introduction to the main areas and also that those readers who are ‘experts’ will find something new to interest them.