AMBIENTUM BIOETHICA BIOLOGIA CHEMIA DIGITALIA DRAMATICA EDUCATIO ARTIS GYMNAST. ENGINEERING EPHEMERIDES EUROPAEA GEOGRAPHIA GEOLOGIA HISTORIA HISTORIA ARTIUM INFORMATICA IURISPRUDENTIA MATHEMATICA MUSICA NEGOTIA OECONOMICA PHILOLOGIA PHILOSOPHIA PHYSICA POLITICA PSYCHOLOGIA-PAEDAGOGIA SOCIOLOGIA THEOLOGIA CATHOLICA THEOLOGIA CATHOLICA LATIN THEOLOGIA GR.-CATH. VARAD THEOLOGIA ORTHODOXA THEOLOGIA REF. TRANSYLVAN
Rezumat articol ediţie STUDIA UNIVERSITATIS BABEŞ-BOLYAI
În partea de jos este prezentat rezumatul articolului selectat. Pentru revenire la cuprinsul ediţiei din care face parte acest articol, se accesează linkul din titlu. Pentru vizualizarea tuturor articolelor din arhivă la care este autor/coautor unul din autorii de mai jos, se accesează linkul din numele autorului.
Autori: RALUCA NICULAE, MARIA MERNEA, LOREDANA GHICA, DAN FLORIN MIHĂILESCU.
DOI: 10.24193/subbchem.2021.3.07
Published Online: 2021-09-30
Published Print: 2021-09-30
pp. 123-139
VIEW PDF
FULL PDF
Acid-sensing ion channel (ASIC) is involved in important processes like synaptic plasticity and learning, fear and anxiety, pain sensation. Due to its role in neurodegeneration and neuroinflammation, the channel is a viable pharmacological target. The channel is activated by acid pH pulses and it rapidly desensitizes; therefore the channel can exist in open, closed and desensitized states. Here we performed a molecular docking study of some ASIC1 ligands like amiloride, cocaine, histamine, ibuprofen, sinomenine and Zn2+ in the transmembrane region of ASIC1 channel models in different states (closed, open and desensitized). Also, since channel properties are influenced by Ca2+, we performed a set of calculations when Ca2+ is present in the channel pore. In addition, we modelled mutant channels in different states with substitutions of residues forming Ca2+ binding sites. The interaction of ligands with mutant channel models was investigated in the presence and absence of Ca2+. Our results show an affinity of ASIC1 for ibuprofen, followed by Zn2+, histamine and amiloride. Sinomenine and cocaine do not appear as ASIC1 ligands regardless of channel state. Overall, Ca2+enhances the interactions of ligands with the channels, including the interactions of cocaine that is not recognized as an ASIC1 ligand. The effect of mutations is to reduce the favourable interactions with ligands. The results obtained on the three channel states are consistent, showing that results are not significantly influenced by the choice of model. Our results bring new information on ASIC1 pharmacological modulation by showing that Ca2+ presence in the pore enhances channel affinity for ligands.
Keywords: ASIC1, molecular docking, protein-ligand interaction, pharmacology
