Molecular modeling method has been used for modeling a new molecule for Breast and colorectal cancer using Topotecan, a drug that’s already designed. This drug is drawn using HYPERCHEM and its R group is modified by replacing different functional groups like OH, CCl2OH, CF2OH, CH2CH2CH3, CH2CH3, CH3, Cl, F, H, and NH2, etc in its place. Molecules designed as such are optimized using different algorithms and their affinity is checked with the protein. The binding free energy of the protein is calculated by performing docking process. The docking process is done with the help of GOLD software. The molecule with minimum binding energy will have the maximum binding affinity. From the results obtained it’s clear that ligand “2(CCl2OH)”has the maximum binding affinity and this molecule is determined as the best lead molecule targets computationally. The calculated binding affinities between inhibitors 1,2,3,4,5,6, 7,8,9,10 are compared. The calculated binding affinities of the inhibitors indicate that inhibitor “2” (CCl2OH) would be expected to be better inhibitor than lead inhibitor 1,3,4,5,6,7,8,9 and 10. Inhibitor “2’’ predicted to be the most potent inhibitor of TOPOTECAN inhibitor as compared to all the other inhibitors considered in this study. For all the cases the minimization results provided qualitative agreement with experimental results. Therefore, this approach could be very useful for screening a larger set of compounds prior to synthesis accordingly; there is a need for methods that enable rapid assessment of large number of structurally unrelated molecules in a reasonably accurate manner. Energy components calculated by performing molecular mechanics calculations both in explicit solvent and complex states are sufficient to estimate the relative binding free energy differences between inhibitors qualitatively.
