FTMove: A Web Server for Detection and Analysis of Cryptic and Allosteric Binding Sites by Mapping Multiple Protein Structures |
| |
| Institution: | 1. Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA;2. Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA;3. Department of Chemistry, Boston University, Boston, MA 02215, USA;1. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA;2. Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA;1. Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK;2. School of Biological and Behavioural Sciences, Queen Mary University of London, London E1 4NS, UK;1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden;2. Science for Life Laboratory, Box 1031, 17121 Solna, Sweden;3. Evi-networks, enskild konsultföretag, Sweden;1. Computational Systems Biology Group, Systems Biology Department, National Center for Biotechnology (CNB-CSIC), c/ Darwin, 3, Madrid 28049, Spain;2. Department of Molecular Biology and Biochemistry, University of Malaga, Malaga 29071, Spain;3. CIBER de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain;4. Institute of Biomedical Research in Malaga (IBIMA), Malaga, Spain;1. Computational Biology Program, The University of Kansas, Lawrence, KS 66047, USA;2. Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, South Kensington, London SW7 2AZ, UK;3. Department of Molecular Biosciences, The University of Kansas, Lawrence, KS 66045, USA |
| |
| Abstract: | Protein mapping distributes many copies of different molecular probes on the surface of a target protein in order to determine binding hot spots, regions that are highly preferable for ligand binding. While mapping of X-ray structures by the FTMap server is inherently static, this limitation can be overcome by the simultaneous analysis of multiple structures of the protein. FTMove is an automated web server that implements this approach. From the input of a target protein, by PDB code, the server identifies all structures of the protein available in the PDB, runs mapping on them, and combines the results to form binding hot spots and binding sites. The user may also upload their own protein structures, bypassing the PDB search for similar structures. Output of the server consists of the consensus binding sites and the individual mapping results for each structure - including the number of probes located in each binding site, for each structure. This level of detail allows the users to investigate how the strength of a binding site relates to the protein conformation, other binding sites, and the presence of ligands or mutations. In addition, the structures are clustered on the basis of their binding properties. The use of FTMove is demonstrated by application to 22 proteins with known allosteric binding sites; the orthosteric and allosteric binding sites were identified in all but one case, and the sites were typically ranked among the top five. The FTMove server is publicly available at https://ftmove.bu.edu. |
| |
| Keywords: | protein binding site allosteric binding drugability binding hot spot protein mapping |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
