From Protein Structure to Function with Bioinformatics.pdf

Prefaceviiof multiple methods within integrated servers. This is more convenient for the userand also allows for determination of consensus predictions. Chapter 10 describesthe resources and operation of ProFunc and ProKnow which work in this way.Chapter 11 discusses published work in which structure-based methods wereapplied to predict functions for Structural Genomics outputs. This results in a valuablepicture of which methods typically prove most informative. The chapter concludeswith a discussion of recent moves towards community annotation as a way to tacklethe bottleneck in annotation of Structural Genomics results. Chapter 12 coversapplications of structure-based methods to model structures, derived by both comparativeand ab initio techniques. As well as a broad range of examples, publishedwork assessing the accuracy of model structures in function-relevant aspects andthe applicability of various methods to model structures is discussed.This book is designed to provide an up-to-date impression of the state-of-the-artin protein structure prediction and structure-based function prediction. Each methodschapter contains links to available servers and other resources which the readermay wish to apply to his or her protein. At the end of each chapter, authors pick outfuture directions and challenges in their respective areas. I hope the reader gains anaccurate impression of the impressive pace of research in these areas. Even whilethis book was being finalised, significant progress in a longstanding problem area– refinement of comparative models – was reported (Jagielska et al. 2008).Nevertheless, it seems that protein structures continually present new challenges tobe met. Just as we may feel that the community is getting to grips with domainswapping, circular permutation, fibril formation and intrinsically disordered proteins,to name but a few previously unexpected phenomena, we are presented withmetamorphic proteins (Murzin 2008) which may carry profound implications forour understanding of protein fold space. Will bioinformatics methods ever be ableto predict which proteins can morph from one fold to another? That remains uncertain,but clearly the bioinformatics of protein structure-function will remain anexciting research area for many years to come.ReferencesJagielska A, Wroblewska L, Skolnick J (2008) Protein model refinement using an optimized physicsbasedall-atom force field. Proc Natl Acad Sci USA 105:8268–8273Lesk AM (1997) CASP2: report on ab initio predictions. Proteins Suppl 1:151–166Murzin AG (2008) Metamorphic proteins. Science 320:1725–1726