Investigation of the tight binding mechanism of a new anticoagulant DD217 to factor Xa by means of molecular docking and molecular dynamics.
| Autor: | Shulga DA; Department of Chemistry, Moscow State University, Moscow, Russia., Tserkovnikova NA; Department of Kinetics and Catalysis, Institute of Chemical Physics of Russian, Academy of Sciences, Moscow, Russia., Tarasov DN; Department of Kinetics and Catalysis, Institute of Chemical Physics of Russian, Academy of Sciences, Moscow, Russia.; PharmaDiall LLC, Moscow, Russia., Tovbin DG; Department of Kinetics and Catalysis, Institute of Chemical Physics of Russian, Academy of Sciences, Moscow, Russia.; PharmaDiall LLC, Moscow, Russia. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023 Jul; Vol. 41 (10), pp. 4723-4734. Date of Electronic Publication: 2022 May 09. |
| DOI: | 10.1080/07391102.2022.2072387 |
| Abstrakt: | A new promising drug candidate DD217 has been proposed recently as a potent anticoagulant acting on factor Xa (fXa) target. It exhibits the lowest concentration of doubling the prothrombin time among the known anticoagulants. In order to explain the efficacy of DD217 in terms of molecular interactions with its target we studied the hypothesis of the tight binding mechanism by means of molecular dynamics simulations and statistical analysis of the trajectory. The conducted analysis confirms the significant contributions to the MM/GBSA estimated binding free energy of the S4 pocket residues as well the crucial role of establishing the hydrogen bonds between the ligand and the backbone amides of Gly216 and Gly218 of the target. The simulation results support the hypothesis of the tight binding mechanism of DD217 to fXa.Communicated by Ramaswamy H. Sarma. |
| Databáze: | MEDLINE |
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