Identification of dihydroorotate dehydrogenase as a protein target of ginkgolic acid by molecular docking and dynamics

Although ginkgolic acids (GAs) are identified as allergenic components in the leaves and seed coat of ginkgo biloba, it is widely revealed that GAs can exhibit various promising biological activities such as anti-tumor activity and antibacterial activity. Thus, investigating molecular targets underlying biological activities of GAs can contribute to the further development and utilization of GAs. In this paper, five kinds of common GAs were prepared for the large-scale reverse docking experiment. The results obtained by network analysis displayed that GAs can directly target at least four important druggable proteins: peroxisome proliferator-activated receptor (PPARA, PPARD, and PPARG), and dihydroorotate dehydrogenase (DHODH). Subsequently, molecular dynamics (MD) simulations and MM/GBSA calculations demonstrated that all the GAs can bind tightly with DHODH thermodynamically, implying that DHODH was probably considered as one of potential protein targets of GAs. Given the clinical significance of DHODH, these bioactive molecules (GAs) could serve as promising therapeutic agents against acute myeloid leukemia (AML) or the starting scaffold for the development of natural DHODH inhibitors. (C) 2020 Elsevier B.V. All rights reserved.