Limits...
Implementing the "Best Template Searching" tool into Adenosiland platform.

Floris M, Sabbadin D, Ciancetta A, Medda R, Cuzzolin A, Moro S - In Silico Pharmacol (2013)

Bottom Line: The tool computes several similarity indexes and sort the outcoming results according to the index selected by the user.We have implemented our web-resource dedicated to ARs Adenosiland with the "Best Template Searching" facility, a tool to guide template and models selection for hARs modelling.The underlying idea of our new facility, that is the selection of a template (or models built upon a template) whose co-crystallized ligand shares the highest similarity with the query structure, can be easily extended to other GPCRs.

View Article: PubMed Central - PubMed

Affiliation: CRS4, Parco Polaris, 09010 Pula, CA Italy.

ABSTRACT

Background: Adenosine receptors (ARs) belong to the G protein-coupled receptors (GCPRs) family. The recent release of X-ray structures of the human A2A AR (h A2A AR ) in complex with agonists and antagonists has increased the application of structure-based drug design approaches to this class of receptors. Among them, homology modeling represents the method of choice to gather structural information on the other receptor subtypes, namely A1, A2B, and A3 ARs. With the aim of helping users in the selection of either a template to build its own models or ARs homology models publicly available on our platform, we implemented our web-resource dedicated to ARs, Adenosiland, with the "Best Template Searching" facility. This tool is freely accessible at the following web address: http://mms.dsfarm.unipd.it/Adenosiland/ligand.php.

Findings: The template suggestions and homology models provided by the "Best Template Searching" tool are guided by the similarity of a query structure (putative or known ARs ligand) with all ligands co-crystallized with hA2A AR subtype. The tool computes several similarity indexes and sort the outcoming results according to the index selected by the user.

Conclusions: We have implemented our web-resource dedicated to ARs Adenosiland with the "Best Template Searching" facility, a tool to guide template and models selection for hARs modelling. The underlying idea of our new facility, that is the selection of a template (or models built upon a template) whose co-crystallized ligand shares the highest similarity with the query structure, can be easily extended to other GPCRs.

No MeSH data available.


Workflow of the homology modeling template selection based on the structure of furan-2-carboxylic acid (4-phenyl-5-pyridin-4-yl-thiazol-2-yl)-amide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4230649&req=5

Fig1: Workflow of the homology modeling template selection based on the structure of furan-2-carboxylic acid (4-phenyl-5-pyridin-4-yl-thiazol-2-yl)-amide.

Mentions: Ligand similarity biased template selection criteria at the basis of the “Best Template Searching” tool has been successfully applied to rationalize the Structure Activity Relationships (SAR) of a series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] furamides as antagonist of the hARs (Inamdar et al. 2013). The most potent derivative of the furamides series, the furan-2-carboxylic acid (4-phenyl-5-pyridin-4-yl-thiazol-2-yl)-amide, has been selected as query molecule: As reported in Table 2, a similarity sorting of the templates based on the combined similarity criteria has been taken into account to select the most suitable models for receptor-based ligand design. The selected workflow is summarized in Figure 1: Starting from the suggested best template, namely the structure with the 3UZA PDB ID, co-crystallized with the 6-(2,6-dimethylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine (T4G), we have constructed A1, A2B and A3 AR models through homology modeling and used the so derived structural information to provide hypotheses of ligand-receptor interaction and ligand-receptor selectivity profile (Inamdar et al. 2013).Figure 1


Implementing the "Best Template Searching" tool into Adenosiland platform.

Floris M, Sabbadin D, Ciancetta A, Medda R, Cuzzolin A, Moro S - In Silico Pharmacol (2013)

Workflow of the homology modeling template selection based on the structure of furan-2-carboxylic acid (4-phenyl-5-pyridin-4-yl-thiazol-2-yl)-amide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230649&req=5

Fig1: Workflow of the homology modeling template selection based on the structure of furan-2-carboxylic acid (4-phenyl-5-pyridin-4-yl-thiazol-2-yl)-amide.
Mentions: Ligand similarity biased template selection criteria at the basis of the “Best Template Searching” tool has been successfully applied to rationalize the Structure Activity Relationships (SAR) of a series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] furamides as antagonist of the hARs (Inamdar et al. 2013). The most potent derivative of the furamides series, the furan-2-carboxylic acid (4-phenyl-5-pyridin-4-yl-thiazol-2-yl)-amide, has been selected as query molecule: As reported in Table 2, a similarity sorting of the templates based on the combined similarity criteria has been taken into account to select the most suitable models for receptor-based ligand design. The selected workflow is summarized in Figure 1: Starting from the suggested best template, namely the structure with the 3UZA PDB ID, co-crystallized with the 6-(2,6-dimethylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine (T4G), we have constructed A1, A2B and A3 AR models through homology modeling and used the so derived structural information to provide hypotheses of ligand-receptor interaction and ligand-receptor selectivity profile (Inamdar et al. 2013).Figure 1

Bottom Line: The tool computes several similarity indexes and sort the outcoming results according to the index selected by the user.We have implemented our web-resource dedicated to ARs Adenosiland with the "Best Template Searching" facility, a tool to guide template and models selection for hARs modelling.The underlying idea of our new facility, that is the selection of a template (or models built upon a template) whose co-crystallized ligand shares the highest similarity with the query structure, can be easily extended to other GPCRs.

View Article: PubMed Central - PubMed

Affiliation: CRS4, Parco Polaris, 09010 Pula, CA Italy.

ABSTRACT

Background: Adenosine receptors (ARs) belong to the G protein-coupled receptors (GCPRs) family. The recent release of X-ray structures of the human A2A AR (h A2A AR ) in complex with agonists and antagonists has increased the application of structure-based drug design approaches to this class of receptors. Among them, homology modeling represents the method of choice to gather structural information on the other receptor subtypes, namely A1, A2B, and A3 ARs. With the aim of helping users in the selection of either a template to build its own models or ARs homology models publicly available on our platform, we implemented our web-resource dedicated to ARs, Adenosiland, with the "Best Template Searching" facility. This tool is freely accessible at the following web address: http://mms.dsfarm.unipd.it/Adenosiland/ligand.php.

Findings: The template suggestions and homology models provided by the "Best Template Searching" tool are guided by the similarity of a query structure (putative or known ARs ligand) with all ligands co-crystallized with hA2A AR subtype. The tool computes several similarity indexes and sort the outcoming results according to the index selected by the user.

Conclusions: We have implemented our web-resource dedicated to ARs Adenosiland with the "Best Template Searching" facility, a tool to guide template and models selection for hARs modelling. The underlying idea of our new facility, that is the selection of a template (or models built upon a template) whose co-crystallized ligand shares the highest similarity with the query structure, can be easily extended to other GPCRs.

No MeSH data available.