Proper determination of agonist efficacy is indispensable in the evaluation of agonist selectivity and bias to activation of specific signalling pathways. The operational model (OM) of pharmacological agonism is a useful means for achieving this goal. Allosteric ligands bind to receptors at sites that are distinct from those of endogenous agonists that interact with the orthosteric domain on the receptor. An allosteric modulator and an orthosteric agonist bind simultaneously to the receptor to form a ternary complex, where the allosteric modulator affects the binding affinity and operational efficacy of the agonist. Allosteric modulators are an intensively studied group of receptor ligands because of their selectivity and preservation of physiological space-time pattern of the signals they modulate. We analysed the operational model of allosterically-modulated agonism (OMAM) including modulation by allosteric agonists. Similar to OM, several parameters of OMAM are inter-dependent. We derived equations describing mutual relationships among parameters of the functional response and OMAM. We present a workflow for the robust fitting of OMAM to experimental data using derived equations.

• MeSH
• alosterická regulace MeSH
• kinetika MeSH
• lidé MeSH
• ligandy MeSH
• receptory spřažené s G-proteiny agonisté   metabolismus   MeSH
• synergismus léků * MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ligandy MeSH
• receptory spřažené s G-proteiny MeSH

• MeSH
• adenosintrifosfát farmakologie   MeSH
• citráty farmakologie   MeSH
• cytosinnukleotidy farmakologie   MeSH
• guaninnukleotidy farmakologie   MeSH
• karboxylyasy antagonisté a inhibitory   metabolismus   MeSH
• kinetika MeSH
• kyselina aspartová farmakologie   MeSH
• nukleotidy farmakologie   MeSH
• papírová chromatografie MeSH
• spektrofotometrie MeSH
• Streptomyces enzymologie   metabolismus   MeSH
• sukcináty farmakologie   MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosintrifosfát MeSH
• citráty MeSH
• cytosinnukleotidy MeSH
• guaninnukleotidy MeSH
• karboxylyasy MeSH
• kyselina aspartová MeSH
• nukleotidy MeSH
• sukcináty MeSH

• MeSH
• adeninnukleotidy farmakologie   MeSH
• adenosintrifosfát farmakologie   MeSH
• citráty MeSH
• lyasy analýza   antagonisté a inhibitory   metabolismus   MeSH
• nukleotidy farmakologie   MeSH
• spektrofotometrie MeSH
• Streptomyces účinky léků   enzymologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adeninnukleotidy MeSH
• adenosintrifosfát MeSH
• citráty MeSH
• lyasy MeSH
• nukleotidy MeSH