TY - JOUR A1 - Sarukhanyan, Edita A1 - Shityakov, Sergey A1 - Dandekar, Thomas T1 - In silico designed Axl receptor blocking drug candidates against Zika virus infection JF - ACS Omega N2 - After a large outbreak in Brazil, novel drugs against Zika virus became extremely necessary. Evaluation of virus-based pharmacological strategies concerning essential host factors brought us to the idea that targeting the Axl receptor by blocking its dimerization function could be critical for virus entry. Starting from experimentally validated compounds, such as RU-301, RU-302, warfarin, and R428, we identified a novel compound 2′ (R428 derivative) to be the most potent for this task amongst a number of alternative compounds and leads. The improved affinity of compound 2′ was confirmed by molecular docking as well as molecular dynamics simulation techniques using implicit solvation models. The current study summarizes a new possibility for inhibition of the Axl function as a potential target for future antiviral therapies. KW - free energy KW - molecular docking KW - molecular dynamics KW - simulation KW - pharmacology KW - proteins KW - structure-activity relationship KW - viruses KW - Zika virus Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176739 VL - 3 IS - 5 ER - TY - JOUR A1 - Bencurova, Elena A1 - Shityakov, Sergey A1 - Schaack, Dominik A1 - Kaltdorf, Martin A1 - Sarukhanyan, Edita A1 - Hilgarth, Alexander A1 - Rath, Christin A1 - Montenegro, Sergio A1 - Roth, Günter A1 - Lopez, Daniel A1 - Dandekar, Thomas T1 - Nanocellulose composites as smart devices with chassis, light-directed DNA Storage, engineered electronic properties, and chip integration JF - Frontiers in Bioengineering and Biotechnology N2 - The rapid development of green and sustainable materials opens up new possibilities in the field of applied research. Such materials include nanocellulose composites that can integrate many components into composites and provide a good chassis for smart devices. In our study, we evaluate four approaches for turning a nanocellulose composite into an information storage or processing device: 1) nanocellulose can be a suitable carrier material and protect information stored in DNA. 2) Nucleotide-processing enzymes (polymerase and exonuclease) can be controlled by light after fusing them with light-gating domains; nucleotide substrate specificity can be changed by mutation or pH change (read-in and read-out of the information). 3) Semiconductors and electronic capabilities can be achieved: we show that nanocellulose is rendered electronic by iodine treatment replacing silicon including microstructures. Nanocellulose semiconductor properties are measured, and the resulting potential including single-electron transistors (SET) and their properties are modeled. Electric current can also be transported by DNA through G-quadruplex DNA molecules; these as well as classical silicon semiconductors can easily be integrated into the nanocellulose composite. 4) To elaborate upon miniaturization and integration for a smart nanocellulose chip device, we demonstrate pH-sensitive dyes in nanocellulose, nanopore creation, and kinase micropatterning on bacterial membranes as well as digital PCR micro-wells. Future application potential includes nano-3D printing and fast molecular processors (e.g., SETs) integrated with DNA storage and conventional electronics. This would also lead to environment-friendly nanocellulose chips for information processing as well as smart nanocellulose composites for biomedical applications and nano-factories. KW - nanocellulose KW - DNA storage KW - light-gated proteins KW - single-electron transistors KW - protein chip Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283033 SN - 2296-4185 VL - 10 ER - TY - JOUR A1 - Sarukhanyan, Edita A1 - Shityakov, Sergey A1 - Dandekar, Thomas T1 - Rational drug design of Axl tyrosine kinase type I inhibitors as promising candidates against cancer JF - Frontiers in Chemistry N2 - The high level of Axl tyrosine kinase expression in various cancer cell lines makes it an attractive target for the development of anti-cancer drugs. In this study, we carried out several sets of in silico screening for the ATP-competitive Axl kinase inhibitors based on different molecular docking protocols. The best drug-like candidates were identified, after parental structure modifications, by their highest affinity to the target protein. We found that our newly designed compound R5, a derivative of the R428 patented analog, is the most promising inhibitor of the Axl kinase according to the three molecular docking algorithms applied in the study. The molecular docking results are in agreement with the molecular dynamics simulations using the MM-PBSA/GBSA implicit solvation models, which confirm the high affinity of R5 toward the protein receptor. Additionally, the selectivity test against other kinases also reveals a high affinity of R5 toward ABL1 and Tyro3 kinases, emphasizing its promising potential for the treatment of malignant tumors. KW - Axl tyrosine kinase KW - anti-cancer drug-like molecules KW - rational drug design KW - molecular docking KW - molecular dynamics Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199505 SN - 2296-2646 VL - 7 IS - 920 ER -