Application of virtual screening and molecular dynamics for the analysis of selectivity of inhibitors of HU proteins targeted to the DNA-recognition site
- Authors: Talyzina A.A.1, Agapova Y.K.2, Podshivalov D.D.2,3,4, Timofeev V.I.2,4, Sidorov-Biryukov D.D.4, Rakitina T.V.2,5
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Affiliations:
- Moscow Institute of Physics and Technology
- National Research Centre “Kurchatov Institute,”
- M. V. Lomonosov Moscow State University
- Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics,”
- Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
- Issue: Vol 62, No 6 (2017)
- Pages: 903-908
- Section: Structure of Macromolecular Compounds
- URL: https://journals.rcsi.science/1063-7745/article/view/191480
- DOI: https://doi.org/10.1134/S1063774517060244
- ID: 191480
Cite item
Abstract
DNA-Binding HU proteins are essential for the maintenance of genomic DNA supercoiling and compaction in prokaryotic cells and are promising pharmacological targets for the design of new antibacterial agents. The virtual screening for low-molecular-weight compounds capable of specifically interacting with the DNA-recognition loop of the HU protein from the mycoplasma Spiroplasma melliferum was performed. The ability of the initially selected ligands to form stable complexes with the protein target was assessed by molecular dynamics simulation. One compound, which forms an unstable complex, was eliminated by means of a combination of computational methods, resulting in a decrease in the number of compounds that will pass to the experimental test phase. This approach can be used to solve a wide range of problems related to the search for and validation of low-molecular-weight inhibitors specific for a particular protein target.
About the authors
A. A. Talyzina
Moscow Institute of Physics and Technology
Author for correspondence.
Email: anna.talyzina@phystech.edu
Russian Federation, Dolgoprudnyi, Moscow oblast, 141701
Yu. K. Agapova
National Research Centre “Kurchatov Institute,”
Email: anna.talyzina@phystech.edu
Russian Federation, Moscow, 123098
D. D. Podshivalov
National Research Centre “Kurchatov Institute,”; M. V. Lomonosov Moscow State University; Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics,”
Email: anna.talyzina@phystech.edu
Russian Federation, Moscow, 123098; Moscow, 119991; Moscow, 119333
V. I. Timofeev
National Research Centre “Kurchatov Institute,”; Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics,”
Email: anna.talyzina@phystech.edu
Russian Federation, Moscow, 123098; Moscow, 119333
D. D. Sidorov-Biryukov
Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics,”
Email: anna.talyzina@phystech.edu
Russian Federation, Moscow, 119333
T. V. Rakitina
National Research Centre “Kurchatov Institute,”; Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
Email: anna.talyzina@phystech.edu
Russian Federation, Moscow, 123098; Moscow, 117997