The binding modes of each compound into the active site of CDK1 were determined using ligand-receptor molecular docking; Glide software from Schrödinger suite was used [25 (link)]. This software has many successful aplications and is widely used for drug discovery [26 (link),27 (link)], structure-activity relationship analysis [28 (link)–30 (link)], virtual screening [31 (link),32 (link)], pharmacophore modeling [33 (link)–35 (link)], evaluation of enzymatic reaction pathways [36 (link),37 (link)], and other studies.
Protein coordinates were extracted from the crystal structure of the complex CDK1-Cyclin bound to an ATP-competitive inhibitor (code 4Y72 in Protein Data Bank) [38 ]. Water molecules inside the active site were deleted before docking experiments to allow each compound to freely find its best pose inside the protein. A grid box of 28Å x 28Å x 28Å was centered on the center of mass of the inhibitor in this crystal structure covering the ATP-binding site of CDK1. To assign ionization states, ring conformations and stereochemistry of the compounds, the module LigPrep was used (LigPrep 3.0, Maestro 10.2.011, Schrödinger LLC). Docking parameters were used as in previous works [28 (link)–30 (link)]. Glide standard (SP) and extra-precision (XP) modes were used. From the found poses, the ones that showed the lower total docking energy (i.e. more favorable pose) were chosen.
Protein coordinates were extracted from the crystal structure of the complex CDK1-Cyclin bound to an ATP-competitive inhibitor (code 4Y72 in Protein Data Bank) [38 ]. Water molecules inside the active site were deleted before docking experiments to allow each compound to freely find its best pose inside the protein. A grid box of 28Å x 28Å x 28Å was centered on the center of mass of the inhibitor in this crystal structure covering the ATP-binding site of CDK1. To assign ionization states, ring conformations and stereochemistry of the compounds, the module LigPrep was used (LigPrep 3.0, Maestro 10.2.011, Schrödinger LLC). Docking parameters were used as in previous works [28 (link)–30 (link)]. Glide standard (SP) and extra-precision (XP) modes were used. From the found poses, the ones that showed the lower total docking energy (i.e. more favorable pose) were chosen.
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