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Inverse Screening @tome server:
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EDMON v1.2 (Endocrine Disruptor MONitoring)
A computational tool to study interactions between nuclear hormone receptors and endocrine-disrupting chemicals
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Principle of the study:
This tool tries to dock your disruptor into structures of receptors taking into consideration the orientation of the crystallographic ligands (anchors) in the templates and their profile of contacts. Screening is made on a database of suitable homologous complexes supports (models or structures) previously calculated with the pipeline @tome.
Exploration of different docking positions is made by the software Plants that calculates multiple conformations by rotation of dihedral angles or ligand translation. A weight is added if the orientation of the candidate ligand is close to a position of a homologous cristallographic ligand. The side chains of residues of the binding sites are not taken into account in the calculation.
For each modeled complex many descriptors are calculated:
- A theoretical affinity (pKd) is calculated using several scoring functions such as MedusaScore, X-score and DSX.
- Similarity with profile of contacts ligand/receptor in homologous crystallographic complexes (PDB).
- Theoretical ligand position error (LPE) is calculated by multiple regression (SVM) with many descriptors.
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A significant correlation with experimental poses as well as with observed binding affinities was obtained.
As shown in the case of the bisphenol A (BPA), bisphenol AF (BPAF), tetra-chloro-bisphenol A (TCBPA) and bisphenol C (BPC) into the estrogen receptor (ERa)
the mode of binding are perfectly reproduced in silico.
Modeled / Measured
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Study Ref: Delfosse et al, PNAS, 2012 - Doi: 10.1073/pnas.1203574109
Atome 2 Server Ref:
Pons & Labesse - Nucleic Acids Research, Web Server Issue- 2009
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