Molecular Dynamics Simulation of VEGFR2 with Sorafenib and Other Urea-Substituted Aryloxy Compounds

Abstract

The binding mode of sorafenib with VEGFR2 was studied using molecular docking and molecular dynamics method. The docking results show that sorafenib forms hydrogen bonds with Asp1046, Cys919, and Glu885 of VEGFR2 receptor. Molecular dynamics simulation suggests that the hydrogen bond involving Asp1046 is the most stable one, and it is almost preserved during all the MD simulation time. The hydrogen bond formed with Cys919 occurs frequently after 6 ns, while the bifurcated hydrogen bonds involving Glu885 occurs occasionally. Meantime, molecular dynamics simulations of VEGFR2 with 11 other urea-substituted aryloxy compounds have also been performed, and the results indicate that a potent VEGFR2 inhibitor should have lower interaction energy with VEGFR2 and create at least 2 hydrogen bonds with VEGFR2.