Structural genomics is a newly emerging field that has arisen following the successful footsteps of the major sequencing efforts generally bundled under the heading genomics. Practical considerations and the diversity of funding mechanisms in different countries have led to different interpretations of what structural genomics actually is. By a strict analogy to sequencing, one might envisage structural genomics to be the determination of the three-dimensional structures of all the proteins coded by a genome. This is an impractical goal because many proteins are not amenable to purification in a form suitable for structure determination, or in fact may be inherently unstructured. Furthermore, the numbers of distinct polypeptides produced in a eukaryotic organism; when one takes into account the possibility of splice variants and posttranslational modification is so large that determining the structures of all forms would be an impossible task at the present time.
The objective of this volume of Methods in Molecular Biology, Structural Proteomics: High-Throughput Methods, is to provide readers with a current view of all aspects of the “pipeline” that takes protein targets to structures and how these have been optimized. Given the wide variety of approaches taken in different laboratories, some individual methods will no doubt have been omitted despite a genuine attempt on the part of the editors and authors to cover their topic areas as widely as possible. This volume includes chapters describing the individual steps in the structural genomics pipeline in depth, as well as less detailed overviews of individual structural genomics initiatives. The overviews give some insight into the diversity of approaches adopted by different laboratories. The chapters are grouped in sections ordered in progression along the structural genomics pipeline: “Protein Target Selection, Bioinformatic Approaches and Data Management,” “Protein Production,” “Biophysical and Functional Characterization of Proteins,” “Structural Characterization of Proteins,” and “Structural Proteomics Initiatives Overviews.” Readers are encouraged to access further details on the methodologies in online resources such as PepcDB (protein expression purification and crystallization database: pepcdb.pdb.org) and the cited literature. It should be emphasized that most methods are as amenable to small laboratories as large consortia, and do not require major investments in facilities. It is hoped that this volume will help smaller laboratories establish high-throughput techniques.
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