2018
Ruthenium Anticancer Drugs and Macromolecular Drug Carriers: Prediction of Binding
DURNÍK, Ivo, Petr KULHÁNEK a Radek MAREKZákladní údaje
Originální název
Ruthenium Anticancer Drugs and Macromolecular Drug Carriers: Prediction of Binding
Autoři
DURNÍK, Ivo, Petr KULHÁNEK a Radek MAREK
Vydání
XIX. Setkání biochemiků a molekulárních biologů, Brno, 2018
Další údaje
Jazyk
angličtina
Typ výsledku
Konferenční abstrakt
Stát vydavatele
Česká republika
Utajení
není předmětem státního či obchodního tajemství
Organizační jednotka
Středoevropský technologický institut
ISBN
978-80-210-9069-9
Změněno: 26. 3. 2019 15:39, Mgr. Pavla Foltynová, Ph.D.
Anotace
V originále
Conventional 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.
Návaznosti
| CZ.1.05/1.1.00/02.0068, interní kód MU |
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