Molecular Modelling: Principles and Applications (2nd Edition)

Book Preface

Molecular modelling used to be restricted to a small number of scientists who had access to the necessary computer hardware and software. Its practitioners wrote their own programs, managed their own computer systems and mended them when they broke down. Today’s computer workstations are much more powerful than the mainframe computers of even a few years ago and can be purchased relatively cheaply. It is no longer necessary for the modeller to write computer programs as software can be obtained from commercial soft­ware companies and academic laboratories. Molecular modelling can now be performed in any laboratory or classroom. This book is intended to provide an introduction to some of the techniques used in molecular modelling and computational chemistry, and to illustrate how these techniques can be used to study physical, chemical and biological phenomena. A major objective is to provide, in one volume, some of the theoretical background to the vast array of methods available to the molecular modeller. I also hope that the book will help the reader to select the most appropriate method for a problem and so make the most of his or her modelling hardware and software. Many modelling programs are extremely simple to use and are often supplied with seductive graphical interfaces, which obviously helps to make modelling techniques more accessible, but it can also be very easy to select a wholly inappropriate technique or method.

Most molecular modelling studies involve three stages. In the first stage a model is selected to describe the intra- and inter molecular interactions in the system. The two most common models that are used in molecular modelling are quantum mechanics and molecular mechanics. These models enable the energy of any arrangement of the atoms and molecules in the system to be calculated, and allow the modeller to determine how the energy of the system varies as the positions of the atoms and molecules change. The second stage of a molecular modelling study is the calculation itself, such as an energy minimisation, a molecular dynamics or Monte Carlo simulation, or a conformational search. Finally, the calculation must be analysed, not only to calculate properties but also to check that it has been performed properly.

The book is organised so that some of the techniques discussed in later chapters refer to material discussed earlier, though I have tried to make each chapter as independent of the others as possible. Some readers may therefore be pleased to know that it is not essential to completely digest the chapters on quantum mechanics and molecular mechanics in order to read about methods for searching conformational space! Readers with experience in one or more areas may, of course, wish to be more selective. I have tried to provide as much of the underlying theory as seems appropriate to enable the reader to understand the fundamentals of each method. In doing so I have assumed some background knowledge of quantum mechanics, statistical mechanics, conformational analysis and mathematics. A reader with an undergraduate degree in chemistry should have covered this material, which shou]d also be familiar to many undergraduates in the final year of their degree course. Full discussion can be found in the suggestions for further reading at the end of each chapter. I have also attempted to provide a reasonable selection of original references, though in a book of this scope it is obviously impossible to provide a comprehensive coverage of the literature. In this context, I apologise in advance if any tech­nique is inappropriately attributed.

The range of systems that can be considered in molecular modelling is extremely broad, from isolated molecules through simple atomic and mo1ecular liquids to polymers, bio­logica1 macromolecules such as proteins and DNA and solids. Many of the techniques are illustrated with examples chosen to reflect the breadth of applications. It is inevitable that, for reasons of space, some techruques must be dealt with in a rudimentary fashion (or not at all), and that many interesting and important applications cannot be described. Molecular modelling is a rapidly developing discipline and has benefited from the dramatic improve­ments in computer hardware and software of recent years Calculations that were major undertakings only a few years ago can now be performed using personal computing facilities. Thus, examples used to indicate the ‘state of the art’ at the time of writing will invariably be routine within a short time.