Even after many years of research by numerous groups, our understanding of protein folding is still not at the stage where the structure of a protein can be predicted from its amino acid sequence alone, even though the experiments of Anfinsen in the 60s demonstrated this should be possible in principle. This second edition of Mechanisms of Protein Folding, like the first, is focused on the experimental study of protein folding. Although only seven years have passed since the first edition, there has been a remarkable expansion in our knowledge of in vitro and in vivo protein folding during this period. There have been the impressive crystal structures of GroEL and other chaperones, and major enhancements in experimental techniques to study protein folding, in particular to look at the very early stages of folding.

The first seven chapters of the book cover the current theoretical models of protein folding, its kinetics and the current experimental methods used to study folding. These are reviews by leading experts in the fields. The first chapter, by Dobson, covers the ‘new’ and ‘old’ views of protein folding, and Chapter 6 looks at the molten globule. These views, which at times can appear contradictory, are merging together and to some extent may be rather like the discussions in quantum theory of whether an entity is a particle or a wave, in which the answer is both! For proteins, the folding behaviour of different folds and the experimental setup may emphasise one of these views more than the others. The other chapters focus on specific experimental techniques and show how experiments have pushed back the boundaries of time so that very early events (sub-millisecond) of protein folding can now be studied.

Two further chapters cover proline isomerisation and disulphide bond formation, the other two major factors controlling the rate of monomeric globular protein folding. Up to this point, the book has essentially concentrated on the folding and stability of monomeric globular proteins, mainly in vitro. The chapters have also contained quite detailed information. Of more interest to the general reader are two chapters that cover recent work on the assembly of multi-subunit structures and the actions of chaperones. It is in the multi-subunit structures chapter that there is a section that discusses membrane protein folding, whose importance I would have thought merited a chapter of its own - although this may reflect the relative paucity of experimental work in this area compared with globular proteins. The chapter on chaperones provides a good overview of the various chaperone families and their functions, and looks at the differences between Archaea and eukaryotes.

Three chapters are devoted to case studies of the folding of three proteins: apomyoglobin, collagen and haemaglutinin. The apomyoglobin case covers a standard globular protein, whereas the other two are more unusual and interesting. The collagen case looks at the ‘folding’ of a non-globular protein, the collagen triple-helix, including the aggregation into fibrils. The haemaglutinin case covers the folding of a large, membrane-attached protein in vivo, in which the protein chain is not completely synthesised before protein folding starts to occur. These last five chapters remind us that there is a lot more to protein structure and the generation of biological function than monomeric globular protein folding, and are much more useful for non-experts in protein folding.

The final chapter covers diseases associated with protein misfolding, including various mutations that cause specific conformational changes leading to disease - for example, sickle-cell haemoglobin and, of course, the prion diseases, in which aggregates of misfolded proteins cause the damage.

This book is a valuable snapshot of the state of experimental studies of protein folding at this time. It provides an excellent example of a book at the frontiers of molecular biology, the title of the series. For this reason it does require some background knowledge of protein folding, both theoretical and experimental - it is not for the uninitiated. As a scientist simulating protein folding in silico, I found it a very useful collation of the experimental data available and a reminder of issues that tend to be ignored.

• © The Company of Biologists Limited 2001