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Quantum analysis/improvement of antipsychotic's docking results
Author(s) -
Nunes Gustavo,
Zanatta Geancarlo,
Bezerra Eveline M.,
Costa Roner F.,
Freire Valder N.,
Gottfried Carmem C.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.810.9
Subject(s) - docking (animal) , molecular mechanics , autodock , eticlopride , haloperidol , chemistry , dopamine receptor d3 , computational chemistry , receptor , stereochemistry , dopamine receptor , molecular dynamics , dopamine , biochemistry , biology , medicine , neuroscience , nursing , sch 23390 , in silico , gene
Research support: CNPq‐Brazil Human dopamine receptors are important targets in treatment of Parkinson's disease and Schizophrenia. Thus, the understanding of the binding mechanisms involving selective ligand agents and dopamine receptors D2 and D3 may contribute to pharmacologic strategies. Recently, we have applied quantum mechanics methods to calculate the contribution of each amino acid residue in the binding pocket of D3 receptor in complex with eticlopride (Zanatta, G et al, 2012). In this study, to understand the mechanism of haloperidol interaction, we employed the Molecular Fractionation with Conjugated Caps (MFCC) followed by quantum calculations to analyze the structure of haloperidol docked in D3 receptor using Autodock 4.0 (Fig 1). It was not possible to obtain the stabilization in total binding energy for a radius of 16 Å (Fig. 2), suggesting that this pose is not yet in the best binding conformation. In order to improve the results, we are performing a series of energy minimization steps using quantum mechanics/molecular mechanics (QM/MM). The establishment of a protocol to improve docking results is important to obtain representative structures of selective ligands to D2 and D3 receptors.