Force Calculations for DNA-PAMAM Dendrimer Interactions from Molecular Dynamics Simulations

Abstract

Polyamidoamine (PAMAM) dendrimers are known to bind and condense plasmid DNA (1,2,3). However, the nature of the interaction between dendrimers and DNA and the mechanism of compaction is not fully understood. Potentials of mean force and forces of interaction were calculated from all-atom umbrella sampling simulations of amine-terminated G3 dendrimers and a 24bp strand of double-stranded DNA. Our simulations show that dendrimers and DNA interact with each other over large distances. Simulations also reveal that even low-generation dendrimers can induce significant bending in DNA and that the dendrimer also deforms considerably upon interaction with the DNA. We compare forces calculated from these simulations with optical tweezer experiments on DNA condensation by dendrimers (3) and propose an explanation for the compaction of DNA by dendrimers observed at forces over 60pN.1. A.U. Bielinska, J.F. Kukowska-Latallo, J.R. Baker, Gene Structure and Expression, 1353, 180 (1997).2. W. Chen, N.J. Turro, D.A. Tomalia, Langmuir, 16, 15 (2000).3. F. Ritort, S. Mihardja. S.B. Smith, C. Bustamante, Phys. Rev. Letters, 96, 118301 (2006).