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Practical computational toolkits for dendrimers and dendrons structure design

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Abstract

Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size.

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Acknowledgements

Nuno Martinho is thankful for the funding from FCT (Fundação para a Ciência e Tecnologia) with a doctoral fellowship (SFRH/BD/87838/2012) and iMed.ULisboa grant (UID/DTP/04138/2013). L.C. Silva acknowledges funding from Investigador FCT 2014 (IF/00437/2014), Portugal. Teresa Barata and Steve Brocchini are grateful for funding from the UK Engineering & Physical Sciences Research Council (EPSRC) for the EPSRC Centre for Innovative Manufacturing in Emergent Macromolecular Therapies. Financial support from the consortium of industrial and governmental users for the EPSRC Centre is also acknowledged. Steve Brocchini is grateful for funding from the National Institute of Health Research (NIHR) Biomedical Research Centre at Moorfields Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, Moorfields Special Trustees, the Helen Hamlyn Trust (in memory of Paul Hamlyn), Medical Research Council, Fight for Sight and Freemasons Grand Charity. Mire Zloh acknowledges support by University of Hertfordshire.

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Authors and Affiliations

  1. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisbon, Portugal

    Nuno Martinho, Liana C. Silva & Helena F. Florindo

  2. Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29/39 Brunswick Square, London, WC1N 1AX, UK

    Nuno Martinho, Steve Brocchini & Teresa Barata

  3. Centro de Química-Física Molecular and Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisboa, Portugal

    Liana C. Silva

  4. School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, AL10 9AB, UK

    Nuno Martinho & Mire Zloh

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  1. Nuno Martinho
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  2. Liana C. Silva
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Correspondence to Teresa Barata or Mire Zloh.

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Martinho, N., Silva, L.C., Florindo, H.F. et al. Practical computational toolkits for dendrimers and dendrons structure design. J Comput Aided Mol Des 31, 817–827 (2017). https://doi.org/10.1007/s10822-017-0041-6

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