Structural Biocomputing and Modeling Center

Research lines and Areas of Interest

The structural bioinformatics are applied to the study of human diseases in which the target can be treated either as a single molecule or as a protein complex, and where the available experimental data can be used to validate the predicted interactions. Spacial cases of study are the following:

1) The protein-protein interactions mediated by SH3 domains are involved in transitory associations that produce multiaggregate complexes, which in turn result in new interactions, the amplification and propagation of the chemical signaling, the regulation of catalityc activity, or facilitate the interaction between membrane and cytoskeleton. For these reasons, the SH3 domains represent plausible and attractive therapeutic targets for pharmacological intervention in a wide range of pathologies, since they appear in ceretain key signal proteins, such as Lyn y Hck in AIDS; Lyn, in allergy and asthma; Gbr2 and Src in breast cancer; p85, Grb2 y Gap in cancer, Abl, Grb2 y CrkL in chronic myelogenous leukemia; p47-phox y p67-phox in inflammatory diseases; Src in osteoporosis; Tec in the myelodysplastic syndrome; Btk in pre B cellular leukemia, etc., as well as the localization and regulation of ionic channels (Na channel in Liddle syndrome, Ca channel regulated by domains SH3-GK or the association of the K channel Kv1.5 with Src tyrosine kinase, etc.

2) Molecular modeling of soluble and membrane protein, in complex with ligand, effectors or expands the available tridimensional data by homology modeling. This technique is used to model complex receptors and channels, as is the case of the TRPV1 or the nicotinic acetylcholine receptor channels, and the sphingosine 1-phosphate receptor, belonging to the G-protein coupled receptor 1 family. The use of homology modeling in combination with Molecular Dynamic approaches allows the simulation of membrane proteins in its native membrane environment, including lipids, water molecules and ions.

3) The combination of Structural Proteomics and Bioinformatics can undergo the creation of structural databases, as ADAN (http://adan-embl.ibmc.umh.es) database, which contains a useful collection of different modular protein domains (SH2, SH3, PDZ, etc.) mainly involved in protein-protein interactions. The database contains more than 2500 entries comprising protein interactions domains, enzymes and derived models that are manually integrated and annotated to provide biological and functional information. The database offers as a novelty the position specific scoring matrices, used to predict optimum ligands and to search putative partners in the entire genome.
Finally, computational protein engeneering can provide putative interactors able to modify/regulate the multiprotein complex behaviour by competition, thus being a useful tool in pharmacological intervention.

Research Keywords

Computational Protein Design
Protein-Protein Interactions
Structural Proteomics
Molecular Modeling of Soluble and Membrane Proteins

Financed Projects

Identificación de ligandos y especificidad de dominios SH3 implicados en patologías humanas.
Bancaja. Ref.: UMH 0042/06. 2006-2007.

Localización de ligandos específicos de dominios SH3 implicados en la formación de complejos multiproteína.
Generalitat Valenciana. Ref.: GV/2007/025. 2007-2009.

Contrato de asesoramiento y asistencia en el desarrollo de la base de datos pública ADAN
Fundación Privada Centro de Regulación Genómica. Ref.: FUNDCRG1.07 A

Contrato de asesoramiento y asistencia en el desarrollo de la base de datos pública ADAN
Fundación Privada Centro de Regulación Genómica. Ref.: FUNDCRG1.08 A

Contrato de asesoramiento y asistencia en el desarrollo de la base de datos pública ADAN
Fundación Privada Centro de Regulación Genómica. Ref.: FUNDCRG1.09 A