Molecular docking study of biocompatible enzyme interactions for removal of indoxyl sulfate (IS), indole-3-acetic acid (IAA), and p-cresyl sulfate (PCS) protein bound uremic toxins

The removal of protein bound uremic toxins (PBUT) from kidney failure patients is an ongoing challenge, as this type of protein tightly binds to viral proteins like human serum albumin (HSA) and makes it difficult to remove during hemodialysis (HD). PBUTs bind to transport protein HSA by electrostatic interaction and/or van der Waals (VDW) forces in human blood, and the low concentrations that are found in plasma. High flux dialysis for PBUT clearance leads to back-filtration and significant loss off efficacy, that in turn are responsible for a high number of HD patient deaths. Therefore, the successful removal of PBUT will solve a crucial problem for HD patients by addressing key challenges and achieving improved HD performance, reducing morbidity rates, and prolonging survival. Continued concerns with toxicity and high concentration of PBUT, p -cresyl sulfate (PCS), indoxyl sulfate (IS), and indole- 3-acetic acid (IAA) were chosen as the investigative foci for this study. The goal was to develop an in depth understanding of the PBUT attachments to HSA chains, by examining the interactions between biocompatible enzymes with those of PBUT for potential removal. Laccases from trametes versicolor and melanocarpus albomyces were selected for this study. Molecular modeling docking was used to examine the interactions between HSA and PCS, IS, and IAA. In addition, interactions between laccases and the PBUTs were reviewed with the aim of gaining a clearer understanding of the functional group responsible for perceived interactions necessary for a more efficient removal . Comparison of the results suggested a favorable removal of PBUTs by fungal laccase from melanocarpus albomyces (3FU9) due to its tendency for polar interactions and the affinity energy. Once the results were ranked by affinity, they revealed that melanocarpus albomyces laccase and IAA have the highest binding affinity of − 7.4 kcal/mol. The carboxylic group of IAA plays a key role in the interaction with laccase enzyme 3FU9 and more IAA binding energy to HSA. Therefore, the major outcome of this research points to Laccase 3FU9 being capable of removing IAA. Graphical abstract