4.3. Molecular Docking

The atomics coordinates of the CDK6 structure were downloaded from the Protein Data Bank (PDB ID - 3NUP) and subsequently optimized for modeling the gap in the structures using the “PRIME” module of Schrödinger [47,48]. The structure of EA was constructed using drawing utilities present in MAESTRO (Maestro, Schrödinger, LLC, New York, NY, 2018) and the geometries of the resultant ligand structure were optimized by JAGUAR [49].

The Autodock 4 was used to perform the docking between the CDK6 and EA [50], generated output in the form of inhibition constant along with the free energy of binding. The Autodock performs rigid docking, which involves the usage of free energy factors for the classification of bound conformation. The energy factors are derived from the combination of the available empirical force field as well as the Lamarckian Genetic Algorithm [50]. In the primary step, the grid dimensions were set to 44 × 54 × 50 Å along with the XYZ directions using the AutoGrid with a spacing of 0.375 Å. The maximum efficiency values were set for the Lamarckian genetic algorithm, with the population control was set to 250 as well as the “longer” intervals, which were used for the energy evaluations. The docking was performed on the cluster of Center for High-Performance Computing (CHPC), South Africa, and 100 bound conformations which were grouped based on 2.0 Å RMSD tolerance were generated for CDK6 and EA system. The DrugScoreX was used for performing the re-scoring of the generated docked conformations [51]. The best scoring docked complex was subjected to the MD simulations.