Discovery of novel and selective inhibitors targeting protein tyrosine phosphatase 1B (PTP1B): Virtual screening and molecular dynamic simulation.

Akyol K., Kilic D.

Computers in biology and medicine, cilt.139, ss.104959, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 139
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.compbiomed.2021.104959
  • Dergi Adı: Computers in biology and medicine
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, CINAHL, Compendex, Computer & Applied Sciences, EMBASE, INSPEC, Library, Information Science & Technology Abstracts (LISTA), MEDLINE
  • Sayfa Sayıları: ss.104959
  • Anahtar Kelimeler: PTP1B, TCPTP, Virtual screening, Molecular dynamic simulations, INSULIN SENSITIVITY, BINDING-SITE, DESIGN, GEMCABENE, OPINION, OBESITY
  • Atatürk Üniversitesi Adresli: Evet

Özet

Protein tyrosine phosphatase 1B (PTP1B) is a promising target for Type II diabetes, obesity, and cancer therapeutics. However, capturing selectivity over T cell protein tyrosine phosphatase (TCPTP) is key to PTP1B inhibitor discovery. Current studies demonstrate that the phosphotyrosine (pTyr) binding site confers selectivity to inhibitors. To identify novel selective inhibitors of PTP1B, drugs in the DrugBank were docked into the active and pTyr site using virtual docking tools. The most suitable drugs were selected based on their docking scores, similarity, and visual results before molecular dynamic simulations were performed. A combination of virtual screening and molecular dynamic simulation approaches indicated that five drugs (DB03558, DB05123, DB03310, DB05446, DB03530) targeting the active and second pTyr binding site of PTP1B could be potential selective inhibitors. This study showed that the hit drugs (experimental, research, and approved) could serve as potential selectivity PTP1B inhibitors and as useful treatments for diabetes and cancer. The hit drugs can be experimentally validated via in vitro molecular testing and in vivo animal testing; alternatively, they can be included in ongoing clinical trials. In addition, more effective molecules can be designed by derivatizing these drugs.