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The construction of a molecular topology file is a prerequisite for any classical molecular dynamics simulation. However, the generation of such a file may be very challenging at times, especially for large supramolecules. While many tools are available to provide topologies for large proteins and other biomolecules, the scientific community researching nonbiological systems is not equally well equipped. Here, we present a practical tool to generate topologies for arbitrary supramolecules: The pyPolyBuilder. In addition to linear polymer chains, it also provides the possibility to generate topologies of arbitrary, large, branched molecules, such as, e.g., dendrimers. Furthermore, it also generates reasonable starting structures for simulations of these molecules. pyPolyBuilder is a standalone command-line tool implemented in python. Therefore, it may be easily incorporated in persisting simulation pipelines on any operating systems and with different simulation engines. pyPolyBuilder is freely available on github: https://github.com/mssm-labmmol/pypolybuilder.

The complexation of quercetin molecules with poly(amidoamine) (PAMAM) dendrimers of generation 0-3 was studied by molecular dynamics simulations. Three main points were addressed: (i) the effect of starting from different initial structures; (ii) the performance of the 2016H66 force field (recently validated in the context of dendrimer simulations) in predicting the experimental drug(quercetin)-loading capacity of PAMAM dendrimers; and (iii) the stability of quercetin-PAMAM complexes and their interactions. Initial structures generated by different restraint protocols led to faster convergence compared to initial structures generated by randomly placing the drug molecules in the simulation box. The simulations yielded meta-stable complexes where the loading numbers have converged to average values and were compared to experimentally obtained values. Once the first meta-stable state was reached, the drug-dendrimer complexes did not deviate significantly throughout the simulation. They were characterized in terms of structural properties, such as the radius of gyration and radial distribution functions. The results suggest that quercetin molecules interact mostly with the internal dendrimer monomers rather than to their surface.

A systematic evaluation of the accuracy of the GROMOS-compatible 2016H66 force field in the simulation of dendrimers is performed. More specifically, the poly(amido amine) (PAMAM) and the poly(propyleneimine) (PPI) are considered because of the availability of experimental data and simulation results in the literature. A total of 36 molecular systems are simulated and the radius of gyration, asphericity, density profiles, and the self-diffusion coefficient are monitored in terms of the generation number and pH (low, medium, and high) condition. Overall, the results support the recommendation of the 2016H66 force field for the simulation of dendrimer systems. The natural building-block based strategy adopted in the definition of 2016H66, together with a careful parametrization of the chemical functional groups to reproduce thermodynamic properties in environments of different polarity, and also the ability to accurately reproduce the expected structural and dynamic features of dendrimers, as shown in the present work, make this force field an attractive option for the simulation of such systems.