W490 Nucleic Acids Research, 2009, Vol. 37, Web Server issue performed for a paralogous but active proteine kinase such as Rop18 using KinDOCK (33), the more divergent Rop2 sequence could not be properly aligned with the older procedure. Thanks to the state-of-the-art fold-recog- nition software embedded in @TOME-2, longer and better SAs are obtained (see: http://abcis.cbs.cnrs.fr/ ATV2/EG/48308/atome.html). Their quality and coverage can be assessed as well as that of the corresponding 3D models. This represents a signiﬁcant improvement over the former server. CONCLUSIONS AND PERSPECTIVES As shown previously for the protein-kinases (22) and as illustrated by the above examples (and other to be found in the HTML documentation), successful combination of sequence–structure comparisons with ligand docking is possible even at very low levels of sequence identity (10–20%) in agreement with recent statistical validations (20). This prompted us to make the methodology easily available through a Web-service. However, new scoring functions for evaluation of SAs, 3D models and protein– ligand complexes shall be implemented to improve rank- ing and prediction reliability using consensus strategies. Similarly, functional information corresponding to the templates shall be displayed. Nevertheless, it should be pointed out that predictions must be always regarded as hypothetical (especially at low level of sequence identity) and as shown in the above examples, should rather serve to guide experimental validations. ACKNOWLEDGEMENTS This study has been supported by the CNRS. We thank all the groups that kindly provided us with databases and with binaries or source codes of the software installed and interfaced in this pipeline. We are indebted to Cathy Royer for careful reading of the manuscript. FUNDING Funding for open access charge: CNRS-INSERM. Conﬂict of interest statement. None declared. REFERENCES 1. 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