A Multi-Level Theoretical Study to Disclose the Binding Mechanisms of Gold(III)-Bipyridyl Compounds as Selective Aquaglyceroporin Inhibitors.

摘要: Structural studies have paved the avenue to a deeper understanding of aquaporins (AQPs), small ancient proteins providing efficient transmembrane pathways for water, uncharged solutes such as glycerol, and possibly gas molecules. Despite numerous studies, their roles in health disease remain be fully disclosed. The recent discovery AuIII complexes potent selective inhibitors aquaglyceroporin isoforms paves way possible therapeutic application. binding human AQP3 inhibitor, cationic complex [Au(bipy)Cl2]+ (Aubipy), protein channel has been investigated here by means multi-level theoretical workflow that includes QM, MD QM/MM approaches. hydroxo was identified prevalent form Aubipy physiological media its studied MD. Both non-covalent coordinative Aubipy–AQP3 adducts were simulated probe role modulation water functionality. electronic structures representative then analysed unveil played metal moiety stabilisation. This study spotlights overall importance three key aspects inhibition: 1) water speciation complex, 2) stability 3) conformational changes induced within pore AuIII. obtained results are expected orient future developments design isoform-selective inhibitors.