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| About Paul Hawkins (OpenEye) |
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Paul Hawkins was born in London, was brought up in various parts of the Midlands, went to university in Southampton and did his Ph.D. at "the home of golf", St. Andrews. After a peripatetic career as a post-doc in the U.S. and Australia he settled, against his better judgement, in New England (Boston) to work in biotech as a medicinal chemist. In this capacity he was involved in a variety of project areas, making a wide range of compounds that successfully poisoned a large number of otherwise completely blameless organisms, but fortunately never himself.
After a number of years at the bench he decided it was time for a change and became an applications scientist for Tripos, covering the New England area. In this capacity he became somewhat familiar with the wonder that is SYBYL. Being an applications scientist proved to be so entertaining that he decided to take the plunge and accept an offer he could not refuse from OpenEye, and left New England for the rather newer New Mexico. Joining OpenEye as their first applications scientist has proven to be consistently amusing in spite of the company’s constant demands that he do something that his boss terms “work”.
In his "spare" time Paul enjoys skiing, opera, cycling and sublimating his homicidal urges by playing first-person shooter games on his Xbox.
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Validation using the RCSB: Good Idea or Bad Idea?
Paul C. Hawkins*, Gregory L. Warren and A. Geoffrey Skillman
Protein-ligand co-complexes from the RCSB database have been used in many studies on the quality of docking and conformer generation. However, due to the poor quality of some of the structures, many of their conclusions are invalid. This paper will discuss pitfalls associated with using structures from the RCSB for comparison or validation purposes. These pitfalls include local problems, such as poor quality fits to electron density (of ligand or protein), highly strained ligand structures and global issues such as lack of consideration of experimental error in the structural data. While nominal resolution has been frequently used for identifying good quality structures from the RCSB, much better assessments of quality can be obtained from global measures such as the diffraction-component precision index (DPI) and local measures including the real-space correlation coefficient. Consideration of these measures is mandatory when assembling a reliable set of structures for validation. Many of the problems associated with using ligand structures from the RCSB are eliminated when using small molecule crystal structures from the CSD, as there is a much greater degree of precision in these structures.
With these issues in mind, datasets for validation of conformer generation applications derived from both the RCSB and the CSD will be presented and the performance of a selection of methods on these datasets will be discussed using a number of different metrics.
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