Dendrimer building toolkit: Model building and characterization of various dendrimer architectures

Abstract

We have developed a graphical user interface based dendrimer builder toolkit (DBT) which can be used to generate the dendrimer configuration of desired generation for various dendrimer architectures. The validation of structures generated by this tool was carried out by studying the structural properties of two well known classes of dendrimers: ethylenediamine cored poly(amidoamine) (PAMAM) dendrimer, diaminobutyl cored poly(propylene imine) (PPI) dendrimer. Using full atomistic molecular dynamics (MD) simulation we have calculated the radius of gyration, shape tensor and monomer density distribution for PAMAM and PPI dendrimer at neutral and high pH. A good agreement between the available simulation and experimental (small angle X-ray and neutron scattering; SAXS, SANS) results and calculated radius of gyration was observed. With this validation we have used DBT to build another new class of nitrogen cored poly(propyl ether imine) dendrimer and study it's structural features using all atomistic MD simulation. DBT is a versatile tool and can be easily used to generate other dendrimer structures with different chemistry and topology. The use of general amber force field to describe the intra-molecular interactions allows us to integrate this tool easily with the widely used molecular dynamics software AMBER. This makes our tool a very useful utility which can help to facilitate the study of dendrimer interaction with nucleic acids, protein and lipid bilayer for various biological applications.

Dynamic design: manipulation of millisecond timescale motions on the energy landscape of Cyclophilin A

“…Molecular dynamic simulations were performed using AMBER16 83 and GROMACS5.0 84 software packages and processed using MDTRAJ. 85 MSMs were built and analysed using PyEMMA 2.3.0.…”

Dynamical Interactions of 5-Fluorouracil Drug with Dendritic Peptide Vectors: The Impact of Dendrimer Generation, Charge, Counterions, and Structured Water

“…This result is consistent with molecular dynamics studies of PAMAM dendrimers. 6 Further detail is provided in Figure S9 of the Supporting Information. It is also worthy of note from the results in Table 3 that the SASA of the dendrimers does not increase linearly in proportion to the number of atoms in the dendrimer.…”

Practical computational toolkits for dendrimers and dendrons structure design

“…pH change) as well as interactions of dendrimers with other molecules [23,[25][26][27][28]. Modelling studies of dendrimers have been conducted using different force fields developed for proteins and small molecules, including CHARMM [29], AMBER [30], CVFF [31], Dreiding [32], GROMOS [33], COMPAS [34] and OPLS [35]. Although these types of molecular modelling studies provide information that corroborate experimental data, it still remains difficult to generate the three dimensional models of relevant dendrimers in silico.…”

“…This is particularly true for larger generations or for non-regular dendrimers or dendrons with complex structures. Several molecular modelling tools are suited to build regular dendrimers and hyper-branched polymers, namely Starmaker (part of Silico toolkit) [36,37], Dendrimer Building Toolkit [30], Dendrimer Builder in Materials Studio [38] and HBP builder [39]. However, there are still opportunities to automate process of generation of the structures of more complex dendrimers or dendrons.…”