Similarly, significant effort is currently being invested into virtual screening of small-molecule libraries using docking methods (Richards, 2002 ). In the current drive towards high-throughput crystallography, a large number of protein–inhibitor complexes need to be refined and evaluated, which increases the need for a high level of automation (Blundell et al., 2002 ). Making these computer programs understand the topology of the drug involved is often a laborious process and, when no structural information is available, prone to errors as bond lengths and angles often have to be guessed (Kleywegt et al., 2003 ). During this process, the drug interacts with different types of software and for each of these types a wide variety of packages are available (Davis et al., 2003 ). The protein–drug interaction then needs to be examined in terms of detailed hydrogen-bonding geometry or other scoring functions (reviewed in Brooijmans & Kuntz, 2003 ). Firstly, coordinates for the drug need to be built or an existing molecule modified, followed by docking of the drug into the active site and/or refinement of a protein–drug complex against X-ray diffraction data. With the rise of structure-based drug-design techniques (reviewed in Davis et al., 2003 ), it is important to have software available which supports the ligand/inhibitor throughout the entire design process.
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