Structure-Based Virtual Screening, Molecular Docking, MolecularDynamics Simulation of VEGF Inhibitors for the Clinical Treatment of Ovarian Cancer

Abstract

VEGF and its receptor play an important role both in physiologic and pathologic angiogenesis, which is identified in ovarian cancer progression and metastasis development. The aim of the present investigation is to identify a potential VEGF inhibitor which is playing a crucial role in stimulating the immunosuppressive microenvironment in tumour cells of ovary and to examine for an effectiveness of identified inhibitor for treatment of ovarian cancer using various In silico approaches. 12 established VEGF inhibitors were collected from various literature. The compound AEE788 displays the great affinity towards the target protein as a result of docking study. AEE78 was further used for structure base virtual screening in order to obtain more structurally similar compound with high affinity. Among the 80 Virtual screened compounds, CID 88265020, explicates much better affinity than established compound AEE788. Based on Molecular Dynamics Simulation, pharmacophore and comparative toxicity analysis of both the best established compound and the best virtual screened compound displayed a trivial variation in associated properties. The virtual screened compound CID 88265020 have the high affinity with the lowest re-rank score, and holds a huge potential to inhibit the VGFR and can be implemented for prospective of future investigations in Ovarian Cancer.