Assessing the structural stability and dynamics of Tinospora Cordifolia alkaloids with AKT1 protein: a molecular dynamics simulation study

The AKT1 protein is an important signaling kinase that participates in gastric disorderrelated pathways. Phytocompounds from Tinospora cordifolia, such as berberine, have gastroprotective properties, although the atomic details and stability of their interaction with AKT1 remain unknown. The purpose of this study is to use molecular dynamics simulations to analyze the structural stability, flexibility, and dynamic behavior of the AKT1 protein in association with four important T. cordifolia alkaloids (berberine, jatrorrhizine, tembetarine, and tinosporine). Molecular dynamics simulations were carried out for 10 ns using the CABSflex 2.0 and iMODS servers. Key parameters studied included rootmeansquare fluctuation (RMSF), deformability, Bfactor, eigenvalues, covariance, and elastic network models. All complexes shown stability throughout the simulation. The berberineAKT1 complex exhibited the best features, with low eigenvalues, restricted variation at the binding site, with strong correlated movements, indicating a stable and rigid binding mode. The MD simulations show that berberine forms the most stable complex with AKT1, effectively constraining its dynamics in a way that promotes inhibition. These findings provide a molecular basis for T. cordifolia's apparent bioactivity and identify berberine as a promising option for further exploration.