In silico design of a peptide receptor for dopamine recognition

Autores organización

• 

  James Oswaldo Guevara Pulido

  Autor

Autores

• Rodriguez-Salazar L
• Cifuentes A

Grupos de investigación

• Investigación en Química Aplicada INQA

  

  Investigador

  James Oswaldo Guevara Pulido

Resumen

Dopamine (DA) is an important neurotransmitter with a fundamental role in regulatory functions related to the central, peripheral, renal, and hormonal nervous systems. Dopaminergic neurotransmission dysfunctions are commonly associated with several diseases; thus, in situ quantification of DA is a major challenge. To achieve this goal, enzyme-based biosensors have been employed for substrate recognition in the past. However, due to their sensitivity to changes in temperature and pH levels, new peptide bioreceptors have been developed. Therefore, in this study, four bioreceptors were designed in silico to exhibit a higher affinity for DA than the DA transporters (DATs). The design was based on the hot spots of the active sites of crystallized enzyme structures that are physiologically related to DA. The affinities between the chosen targets and designed bioreceptors were calculated using AutoDock Vina. Additionally, the binding free energy, ?G, of the dopamine-4xp1 complex was calculated by molecular dynamics (MD). This value presented a direct relationship with the E_refine value obtained from molecular docking based on the ?G functions obtained from MOE of the promising bioreceptors. The control variables in the design were amino acids, bond type, steric volume, stereochemistry, affinity, and interaction distances. As part of the results, three out of the four bioreceptor candidates presented promising values in terms of DA affinity and distance. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

• Amino Acid Sequence; Binding Sites; Catalytic Domain; Dopamine; Drug Design; Hydrogen Bonding; Ligands; Molecular Docking Simulation; Molecular Dynamics Simulation; Protein Binding; Receptors, Peptide; Structure-Activity Relationship; dopamine; ligand; protein binding; receptor; amino acid sequence; binding site; chemistry; drug design; enzyme active site; hydrogen bond; metabolism; molecular docking; molecular dynamics; structure activity relation