title: Molecular Dynamics Study of the Structure, Flexibility, and Hydrophilicity of PETIM Dendrimers: A Comparison with PAMAM Dendrimers.
abstract: A new class of dendrimers, the poly(propyl ether imine) (PETIM) dendrimer, has been shown to be a novel hyperbranched polymer having potential applications as a drug delivery vehicle. Structure and dynamics of the amine terminated PETIM dendrimer and their changes with respect to the dendrimer generation are poorly understood. Since most drugs are hydrophobic in nature, the extent of hydrophobicity of the dendrimer core is related to its drug encapsulation and retention efficacy. In this study, we carry out fully atomistic molecular dynamics (MD) simulations to characterize the structure of PETIM (G2-G6) dendrimers in salt solution as a function of dendrimer generation at different protonation levels. Structural properties such as radius of gyration (Rg), radial density distribution, aspect ratio, and asphericity are calculated. In order to assess the hydrophilicity of the dendrimer, we compute the number of bound water molecules in the interior of dendrimer as well as the number of dendrimer-water hydrogen bonds. We conclude that PETIM dendrimers have relatively greater hydrophobicity and flexibility when compared with their extensively investigated PAMAM counterparts. Hence PETIM dendrimers are expected to have stronger interactions with lipid membranes as well as improved drug encapsulation and retention properties when compared with PAMAM dendrimers. We compute the root-mean-square fluctuation of dendrimers as well as their entropy to quantify the flexibility of the dendrimer. Finally we note that structural and solvation properties computed using force field parameters derived based on the CHARMM general purpose force field were in good quantitative agreement with those obtained using the generalized Amber force field (GAFF).
authors.affiliation: Center for Condensed Matter Theory, Department of Physics, Indian Institute of Science , Bangalore, 560012, India.|Department of Chemical Engineering, Center for Biosystems Science and Engineering, Indian Institute of Science , Bangalore, 560012, India.
authors.forename: Subbarao
authors.initials: S
authors.lastname: Kanchi
authors.affiliation: Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology , Hyderabad, 500032, India.
authors.forename: Gorle
authors.initials: G
authors.lastname: Suresh
authors.affiliation: Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology , Hyderabad, 500032, India.
authors.forename: U Deva
authors.initials: UD
authors.lastname: Priyakumar
authors.affiliation: Department of Chemical Engineering, Center for Biosystems Science and Engineering, Indian Institute of Science , Bangalore, 560012, India.
authors.forename: K G
authors.initials: KG
authors.lastname: Ayappa
authors.affiliation: Center for Condensed Matter Theory, Department of Physics, Indian Institute of Science , Bangalore, 560012, India.
authors.forename: Prabal K
authors.initials: PK
authors.lastname: Maiti