(597d) Developing a Coarse-Grained Model for Rosette Nanotubes
AIChE Annual Meeting
2020
2020 Virtual AIChE Annual Meeting
Engineering Sciences and Fundamentals
Molecular Simulation and Modeling of Complex Molecules
Thursday, November 19, 2020 - 8:45am to 9:00am
Rosette nanotubes (RNTs) are biocompatible supramolecular nanostructures that are formed via self-assembly of building blocks of Watson-Crick DNA-inspired guanine-cytosine (G∧C) motifs. Similar to the double helix of DNA, hydrogen bonding between the individual motifs lead them to assemble into rings, called rosettes.1,2 A combination of π-π interactions between the rings and hydrophobic effects lead the rosettes to self-assemble into nanotubes. There are 2 types of RNTs, depending on how the nanotube is self-assembled: either the rings are stacked or they are assembled into helical coils. Because of its biocompatibility, RNTs have attracted attention for drug delivery and biological applications, such as encapsulating dexamethasone to enhance cell growth in bones.3 More recently, RNTs have showed potential in selective transport of ions through lipid bilayers and as single-molecule sensors.4 However, a fundamental understanding of the interactions of RNTs with cell membranes, proteins and other biomolecules could lead to the development of optimal RNTs for these applications. In this work we are developing a coarse-grained model of these RNTs based on the MARTINI force-field,5 reparameterized against all-atom potential of mean force (PMF) calculations. Here, we present details of our coarse-grained model of the G∧C motifs, and report classical molecular dynamics simulations of individual motifs, rosettes and small RNTs, aiming at studies related to drug delivery,3 selective transport of ions and single-molecule sensing.4
1. H. Fenniri, B. L. Deng, and A. E. Ribbe. J. Am. Chem. Soc. 2002, 124, 11064-11072.
2. H. Fenniri, B. L. Deng, A. E. Ribbe, K. Hallenga, J. Jacob, and P. Thiyagarajan, Proc. Natl. Acad. Sci. USA 2002, 99, 6487-6492.
3. G. Borzsonyi, R. Johnson, A. Myles, J. Cho, T. Yamazaki, R. Beingessner, A. Kovalenko, and H. Fenniri. Chem. Commun., 2010, 46, 6527-6529.
4. P. Tripathi, L. Shuai, H. Joshi, H. Yamazaki, W. H. Fowle, A. Aksimentiev, H. Fenniri, M. Wanunu. J. Am. Chem. Soc. 2020, 142, 1680-1685.
5. J. Uusitalo, H. Ingólfsson, P. Akhshi, D. Tieleman, and S. Marrink. J. Chem. Theory Comput., 2015, 11, 3932–3945.