Recent advances in structure-based drug design and virtual screening of VEGFR tyrosine kinase inhibitors

• Review of virtual screening (VS) in discovery of VEGFR2 inhibitors is presented.
• Structural features are derived by co-crystal of VEGFR2 in complex with inhibitors.
• Pharmacophore models and binding modes of applied in VS of VEGFR2 inhibitors.
• Combined VS methods are used effectively in parallel and/or in sequential.

During the past decade, developments in computational processing and X-ray crystallography have allowed virtual screening become integrated into drug discovery campaigns. This review focuses on the recent advancements in the drug discovery of VEGFR2 tyrosine kinase inhibitors (VEGFR2 TKIs) by using in silico methodologies. An introduction for the methodology framework of pharmacophore modeling, molecular docking and structure-based design are provided. We discuss the recent studies on the structures of VEGFR2 protein kinase in different binding modes, and the insights on molecular interactions gained from knowledge of the co-crystal structures complex with structurally diverse VEGFR2 inhibitors. We provide some aspects of model construction and molecular docking techniques. Several representative examples of successful applications on VEGFR2 virtual screening for hit discovery, lead optimization and structure-based design are also presented.