Computational Study Of The Interaction Between PAMAM Dendrimers And Peptides

Understanding the interactions between dendrimers and trans-membrane proteins issignificantly important to optimize the dendrimers for drug delivery and gene transfection.Coarse-grained molecular dynamics simulations within in the framework of MARTINIforce field were employed to study the G4poly (amidoamine)(PAMAM) dendrimerinteracting with the lysine-flanked (KALP) peptide. The influence of KALP peptide on thestructure of the dendrimer under the neutral and acidic pH conditions was considered. Theradius of gyration, shape factor, and radial distribution function of the dendrimer wereanalysed. Meanwhile, the free energy between molecules was calculated. It was found thatthe peptide provide a slight effect on the size and density profile of the dendrimer under thetwo pH conditions, which implies that there exists enough space in the interior of thedendrimer for the KALP peptide penetration. The dendrimer keeps sphere-like shape as thepeptide approaches from the center-of-mass distance of5.0nm to1.0nm. The results ofpotential of mean force between two molecules imply that the dendrimer repels the peptideat low pH possibly due to the steric interaction and electrostatic repulsion. At neutral pH, astable complex of two molecules is also hard to form under the influence of thermalfluctuation. The finding suggests PAMAM dendrimer is unfavourable to absorb theKALP-like trans-membrane proteins.We also simulated the interaction between dendrimer and Amyloid fibril under theneutral and acidic pH conditions. We find the shape of dendrimers changes much when theAmyloid fibril approaches from the center-of-mass distance of5.0nm to1.0nm. Theresults of potential of mean force between two molecules imply that dendrimer repels thepeptide at low pH and they can form a stable complex in neutral pH.