论文部分内容阅读
Transthyretin (TTR) aggregation-associated proteotoxicity arouses several human amyloid diseases.Small molecules binding to TTR prefer stabilization of the tetrameric state of TTR over the dissociative transition state.Kinetic stabilization on TTR can prevent aggregation.This is an effective strategy to halt TTR relevant diseases.To design new promising inhibitors, it is beneficial to understand the interaction between TTR and ligand.A theoretical study was carried out on TTR diclofenac rerial inhibitors, which includes docking, molecular dynamics, binding free energy by MM/PBSA and MM/GBSA methods.Nine ligands interacting with TTR was involved.The results indicate that MM/PBSA performed better in binding free energies than MM/GBSA.The binding free energies calculated by MM/PBSA method has a better correlations than that calculated by MM/PBSA method.