The orientation of asparagine, glutamine and histidine side chains, as well as the position of water molecules should be considered with caution since their determinations remain challenging for X-ray crystallography ( 16). For instance, some atoms in the flexible part of the protein are not resolved and the corresponding spatial coordinates omitted in the PDB file. Despite the methodological improvements in this field, most of these structures usually do not meet the quality criteria required for a modeling study. Of total, 87% of those available in the most comprehensive resource, the Protein Databank, have been obtained by X-ray crystallography. For example, several β-secretase (BACE) and HIV-1 protease (HIV-1 PR) inhibitors have been identified by such a combination ( 12, 13).įirst, a docking assay requires the structure of a target protein. Lastly, docking predictions can be post-processed using free energy calculations. For instance, a recent MD simulation study allowed a better understanding of the molecular switch involving the helix 12 of the peroxisome proliferator-activated receptor alpha ( 11). The properties of the predicted complex can also be investigated by further calculations, so that complex recognition mechanisms might be unveiled. In addition, by docking the same compound into several protein targets, one can gain insights into the underlying molecular mechanisms of selectivity ( 10). Conversely, a small molecule interacting with a protein can be modified in order to change its affinity and, in fine, its biological activity to obtain new molecular probes or drugs ( 3–9). In the context of protein engineering, for instance, the prediction of the detailed molecular interactions between a protein and one of its interacting partners paves the way for the rational selection of amino acids that could be mutated to promote or disrupt this interaction ( 1, 2). Docking programs intrinsically have a wide range of applications that go far beyond the creation of simple visual illustrations. The prediction of such interactions, by so-called docking software, is a non-trivial task. Nowadays, it is well known that most of the processes in life sciences involve, at the atomic scale, complex interactions between at least two molecules. We believe it constitutes a step toward generalizing the use of docking tools beyond the traditional molecular modeling community.īack in the 19th century, Emil Fischer introduced the lock-and-key model to explain enzyme specificity. The SwissDock web site is available online at. ![]() A wiki and a forum are available to the community to promote interactions between users. The web site also provides an access to a database of manually curated complexes, based on the Ligand Protein Database. For automated docking tasks, a programmatic SOAP interface has been set up and template programs can be downloaded in Perl, Python and PHP. An efficient Ajax/HTML interface was designed and implemented so that scientists can easily submit dockings and retrieve the predicted complexes. ![]() It is based on the EADock DSS engine, combined with setup scripts for curating common problems and for preparing both the target protein and the ligand input files. This article presents SwissDock, a web server dedicated to the docking of small molecules on target proteins. Docking programs have a wide range of applications ranging from protein engineering to drug design. The prediction of such interactions at the molecular level, by so-called docking software, is a non-trivial task. Most life science processes involve, at the atomic scale, recognition between two molecules.
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