Structural Bioinformatics, 2nd Edition

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COMPUTATIONAL ASPECTS OF HIGH-THROUGHPUT CRYSTALLOGRAPHIC MACROMOLECULAR STRUCTURE DETERMINATION

Paul D. Adams, Ralf W. Grosse-Kunstleve, and Axel T. Brunger

INTRODUCTION

The desire to understand biological processes at a molecular level has led to the routine application of X-ray crystallography. However, significant time and effort are usually required to solve and complete a macromolecular crystal structure. Much of this effort is in the form of manual interpretation of complex numerical data using a diverse array of software packages and the repeated use of interactive three-dimensional graphics. The need for extensive manual intervention leads to two major problems: significant bottlenecks that impede rapid structure solution (Burley et al., 1999) and the introduction of errors due to subjective interpretation of the data (Mowbray et al., 1999). These problems present a major impediment to the success of structural genomics efforts (Burley et al., 1999; Montelione and Anderson, 1999) that require the whole process of structure solution to be as streamlined as possible. See Chapter 40 for a detailed description of structural genomics. The automation of structure solution is thus necessary as it has the opportunity to produce minimally biased models in a short time. Recent technical advances are fundamental to achieving this automation and make high-throughput structure determination an obtainable goal.

HIGH-THROUGHPUT STRUCTURE DETERMINATION

Automation in macromolecular ...