Vinod Seba Merin, Murugan Sreedevi Sangeetha, Krishnan Anju, Ravichandran Keerthiga, Karthikeyan Pradeep, Kotteswaran Bharath, Rajendran Kumaran
Department of Chemistry, Dwaraka Doss Goverdhan Doss Vaishnav College (Autonomous) (Affiliated to University of Madras), 833, Gokul Bagh, E.V.R. Periyar Road, Arumbakkam, Chennai 600106, Tamil Nadu, India.
Department of Chemistry, Sathyabama Institute of Science and Technology, Kamaraj Nagar, Semmancheri, Chennai 600119, Tamil Nadu, India.
ACS Omega. 2023 Feb 3;8(6):5634-5654. doi: 10.1021/acsomega.2c07111. eCollection 2023 Feb 14.
Molecular docking (Mol.Doc) techniques were employed to ascertain the binding affinity of two resorcinol-based acridinedione dyes (ADR1 and ADR2) with the widely studied globular protein Bovine Serum Albumin (BSA) in the presence of site-selective binding drugs by Autodock Vina 4.2 software. Docking of various feasible conformers of ADR1 dye with BSA was found to be energetically more favored than ADR2 dye, even though both these dyes differ in the 9th position of the basic dye structure. Analysis of dyes with BSA establishes the location of dye in all of the binding sites of BSA, predominantly through conventional and nonconventional hydrogen-bonding (HB) interactions. The coexistence of hydrophobic interactions resulted in the stability of various conformers generated. The introduction of site I and site II (Sudlow site binding drugs) into ADR1-BSA and ADR2-BSA complexes effectively destabilizes the dye-protein complex; however, the drugs do not displace ADR dyes completely from their selective binding domains. Site II binding drugs effectively destabilize the binding ability of the dye-protein complex rather than site I drugs. However, docking of site I drug 3-carboxyl-4-methyl-5-propyl-2-furanpropanic acid (CMPF) largely destabilizes the ADR1-protein complex, whereas indomethacin (INDO) enhances the binding affinity of the ADR2-protein complex. Interestingly, simultaneous docking of ADR dyes to the BSA-drug complex results in larger stability of the protein-drug complex through HB interactions rather than hydrophobic interactions. Both ADR1 and ADR2 dyes predominantly occupy the Sudlow binding sites of BSA, and the introduction of either site I or site II binding drugs does not displace the dye efficiently from the corresponding binding sites, rather the drugs are effectively displaced toward other binding domains apart from their specific site-binding domains of BSA. Through Mol.Doc techniques, we authenticate that the interactions in host-guest complex systems involving competing ligands are established in depth, wherein the dye as well as the amino acid (AA) moieties in BSA act as both HB donor and acceptor sites apart from several hydrophobic interactions coexisting toward the stability.
利用分子对接（Mol.Doc）技术，通过Autodock Vina 4.2软件，在存在位点选择性结合药物的情况下，确定了两种基于间苯二酚的吖啶二酮染料（ADR1和ADR2）与广泛研究的球状蛋白牛血清白蛋白（BSA）的结合亲和力。发现ADR1染料与BSA的各种可行构象的对接在能量上比ADR2染料更有利，尽管这两种染料在碱性染料结构的第9位有所不同。对染料与BSA的分析确定了染料在BSA所有结合位点中的位置，主要是通过传统和非传统的氢键（HB）相互作用。疏水相互作用的共存导致了所产生的各种构象的稳定性。将位点I和位点II（Sudlow位点结合药物）引入ADR1-BSA和ADR2-BSA复合物中有效地破坏了染料-蛋白质复合物的稳定性；然而，这些药物并没有将ADR染料完全从其选择性结合域中取代。位点II结合药物比位点I药物更有效地破坏染料-蛋白质复合物的结合能力。然而，位点I药物3-羧基-4-甲基-5-丙基-2-呋喃丙酸（CMPF）的对接在很大程度上破坏了ADR1-蛋白质复合物的稳定性，而吲哚美辛（INDO）增强了ADR2-蛋白质复合物的结合亲和力。有趣的是，ADR染料与BSA-药物复合物的同时对接通过HB相互作用而不是疏水相互作用导致蛋白质-药物复合物具有更大的稳定性。ADR1和ADR2染料主要占据BSA的Sudlow结合位点，并且引入位点I或位点II结合药物都不能有效地将染料从相应的结合位点上取代，相反，药物被有效地转移到除了它们在BSA的特定位点结合域之外的其他结合域。通过Mol.Doc技术，我们证实了在涉及竞争配体的主客体复合系统中的相互作用得到了深入研究，其中染料以及BSA中的氨基酸（AA）部分除了存在几种有助于稳定性的疏水相互作用外，还作为HB供体和受体位点。
