Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Discovery of New Candidates Targeting the SH2 Domains of Spleen Tyrosine Kinase (Syk) Through in Silico Studies(Wiley-VCH Verlag GmbH, 2025-06) Sansacar, Merve; Sari, Ceyhun; Yucel, Muhsin Samet; Akcok, Emel Basak Gencer; Akcok, Ismail; Gencer Akçok, Emel BaşakSrc homology 2 (SH2) domains have become an increasingly popular candidate for researchers to search for novel therapeutics to target different diseases. Spleen tyrosine kinase (Syk) is one of the proteins with two SH2 domains that has a role in the pathogenesis of many diseases. Here, we report the discovery of a promising natural product (NP) inhibitor that targets the N-terminal SH2 (N-SH2) and C-terminal SH2 (C-SH2) domains of Syk simultaneously, through structure-based drug discovery approach. Molecular docking studies, followed by molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations, were utilized to reveal the interactions between NPs from "the COlleCtion of Open NatUral producTs (COCONUT)" database and Syk enzyme. Five natural products that have lowest Scoring and Minimization with AutoDock Vina (SMINA) scores against both SH2 domains of Syk were selected for further studies and compound CNP0265345 has the best binding free energies toward both C-SH2 and N-SH2 of Syk enzyme with -44.54 and -55.98 kcal/mol, respectively. Drug-likeness properties, absorption, distribution, metabolism, and excretion (ADME) and carcinogenicity predictions were also studied. In conclusion, our work highlights a novel drug candidate to target the Syk enzyme of SH2 domains using in silico methods.Article Citation - WoS: 3Citation - Scopus: 3Determination of Promising Inhibitors for N-SH2 Domain of SHP2 Tyrosine Phosphatase: An in Silico Study(Springer, 2024-05-13) Akcok, Emel Basak Gencer; Guner, Huseyin; Akcok, Ismail; Gencer Akçok, Emel BaşakThere are many genes that produce proteins related to diseases and these proteins can be targeted with drugs as a potential therapeutic approach. Recent advancement in drug discovery techniques have created new opportunities for treating variety of diseases by targeting disease-related proteins. Structure-based drug discovery is a faster and more cost-effective approach than traditional methods. SHP2 phosphatase, encoded by the PTPN11 gene, has been the focus of much attention due to its involvement in many types of diseases. The biological function of SHP2 is enabled mostly by protein-protein interaction through its SH2 domains. In this study, we report the identification of a potential small molecule inhibitor for the N-SH2 domain of SHP2 by structure-based drug discovery approach. We utilized molecular docking studies, followed by molecular dynamics simulations and MM/PBSA calculations, to analyze compounds retrieved from the Broad's Drug Repurposing Hub and ZINC15 databases. We selected 10 hit compounds with the best docking scores from the libraries and examined their binding properties in the N-SH2 domain. We found that compound CID 60838 (Irinotecan) was the most suitable compound with a binding free energy value of - 64.45 kcal/mol and significant interactions with the target residues in the domain.