4.4. Molecular Modeling and Docking Studies

Crystal structure of human kinesin Eg5 with a new monastrol-based inhibitor (R)-mon97 binding (PDB ID 2IEH) was downloaded from RCSB Protein Data Bank (http://www.rcsb.org/pdb). The receptor and the ligands were pretreated. For receptor (2IEH) preparation, water molecules were removed, the hydrogen atoms were added and partial charges were assigned based on the CHARMm force field. For ligand preparation, 3D structures of the ligands were generated in Discovery Studio 4.1 and then energy minimization was performed by the CHARMm force field. Finally, the semiflexible (the receptor was rigid, whereas the ligands were flexible during the docking process) docking mode CDOCKER was used to run the docking program in Discovery Studio 4.1 (Laboratory of CADD, Hainan University, China) with the binding sites (coordinates x, 38.4271, y, 14.1162 and z, 100.177) and receptor radius of 11.4 Å. After molecular docking, conformation on the lowest CDOCKER interaction energy pose was selected as the most probable binding conformation and the docking results were studied with CDOCKER energy scores, CDOCKER interaction energy scores, hydrogen bond interaction and the binding mode pattern.