Investigation of Compounds Found in Ginger (<i>Curcuma longa L</i>.) as Inhibitors for PTP1B for the Treatment of Type 2 Diabetes Using Molecular Docking and Molecular Dynamics Approaches

Abstract Although it is known that insulin resistance is caused by defects in insulin signaling, the underlying mechanisms are not known in detail. Protein–tyrosine phosphatase 1B, a negative regulator of leptin and insulin signaling pathways, is known to be an effective target in the treatment of type 2 diabetes. This study involves the screening of 30 natural compounds found in ginger as an alternative drug against protein‐tyrosine phosphatase 1B by means of molecular docking, molecular dynamics and MM‐PB(GB)/SA methods. 12 compounds had comparable docking scores (−5.7 kcal/mol to −9.2 kcal/mol) compared to the available protein–tyrosine phosphatase 1B inhibitors with docking scores −8.9, −9.4, and −10.0 kcal/mol. In addition to promising docking results, molecular dynamics and binding free energy calculations approved that ginger compounds could have inhibition effects on protein–tyrosine phosphatase 1B enzyme, where 22M2 ligands showed the best binding with the value of −43.42 kcal/mol according to MM–PBSA method. As a result, some compounds from natural sources may serve models for the drug design against protein–tyrosine phosphatase 1B, which is an important target in the treatment of type 2 diabetes.