Rossino, Giacomo published the artcileNew Insights into the Opening of the Occluded Ligand-Binding Pocket of Sigma1 Receptor: Binding of a Novel Bivalent RC-33 Derivative, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is human Sigma1 receptor ligand binding pocket opening RC33 derivative.
Significant progresses have been made to understand the mol. basis of the Sigma1 receptor (S1R) operating in normal and pathol. conditions. S1R is a transmembrane protein that participates in a wide variety of processes at the central nervous system; hence, its function has been associated with mental and neurol. disorders. Several ligands have been proposed to regulate the function of S1R revealing a high plasticity of the ligand-binding pocket. Previous drug-design studies have been mainly based on pharmacophore models; however, the recently revealed crystal structure of S1R provides an excellent opportunity for verifying previous predictions and for evaluating the binding of novel compounds Interestingly, the crystal structure shows that the binding pocket of S1R is highly occluded from solvent; therefore, it is not clear how ligands access this site. In the present work, we applied steered mol. dynamics (SMD) simulations to open the occluded ligand-binding pocket in the S1R crystal structure and to determine the preferred ligand pathway to enter and exit the binding site. The intracellular surface of the β-barrel ligand-binding region was found the most favorable route to accommodate ligands. This route supports the binding of RC-33 (our inhouse-developed S1R modulator) and a new bivalent derivative that constitutes the first divalent structure showed to interact with S1R. Free energy calculations of these compounds associated to S1R agree with exptl. Ki values and provide mol. insights of the binding mode of modulators that could access the S1R ligand-binding pocket through the cytoplasmic region.
Journal of Chemical Information and Modeling published new progress about Central nervous system. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate.
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem