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@proceedings{1514916,
author = {Durník, Ivo and Kulhánek, Petr and Marek, Radek},
booktitle = {2nd Users Conference of IT4Innovations, Ostrava},
language = {eng},
title = {Prediction of Binding of Ruthenium Anticancer Drugs into Macromolecular Drug Carriers},
year = {2018}
}
TY - CONF
ID - 1514916
AU - Durník, Ivo - Kulhánek, Petr - Marek, Radek
PY - 2018
TI - Prediction of Binding of Ruthenium Anticancer Drugs into Macromolecular Drug Carriers
N2 - onventional chemotherapy is complicated by inefficient drug delivery and severe side effects. These shortcomings can be suppressed by newly developed anticancer drugs containing ruthenium, which can be further improved by macromolecular drug carriers. In this work, we investigated the binding of the potential ruthenium(III) anticancer drug into cucurbit[7]uril (CB[7]) as a model of a drug carrier. Calculated free energy using the ABF method and GAFF2 force filed led to a severe overestimation of the binding affinity due to the inappropriate parameters for Lennard-Jones (LJ) potentials. Thus, a library of anchor molecules with known affinity for CB[7] cavity was prepared and characterized employing DFT quantum chemical methods. LJ potentials were then reparametrized to reproduce the DFT binding energies. Newly developed LJ parameters demonstrate significant improvement resulting in a reduction of the error on theoretically predicted binding affinities from 8.6 kcal mol−1 with GAFF2 to 1.2 kcal mol−1 (both results include standard state, entropy, and PMF corrections). New force filed parameters thus open new directions for accurate in silico modeling of supramolecular complexes between CB[7] and modified ruthenium drugs substituted with various anchors.
ER -
DURNÍK, Ivo, Petr KULHÁNEK a Radek MAREK. Prediction of Binding of Ruthenium Anticancer Drugs into Macromolecular Drug Carriers. In \textit{2nd Users Conference of IT4Innovations, Ostrava}. 2018.
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