Comprehensive molecular docking and molecular dynamics simulation study of unmodified and modified cyclodextrins: erlotinib inclusion complexes

The goal of this study is to evaluate the effectiveness of cyclodextrins (CDs) in enhancing the stability and bioavailability of Erlotinib (Erl), while also minimising its side effects, in the treatment of metastatic pancreatic and lung cancers. Molecular docking and molecular dynamics (MD) simulations were employed to investigate the effectiveness of various pure CDs (Alpha, Beta, and Gamma Cyclodextrins) and modified CDs (hydroxypropyl, methyl, and amino Beta Cyclodextrins) in forming stable inclusion complexes (ICs) with Erl. Molecular docking results indicated that Erl displayed favourable binding affinities with all CDs, exhibiting the highest affinity with Gamma Cyclodextrin (GCD) due to its larger cavity, with a binding energy of −25.86 KJ/mol. MD simulations revealed a reduction in hydrogen bonds with solvent molecules in CD complexes compared to free CDs, indicating the successful inclusion of Erl into CD cavities. GCD exhibited the highest EVdw and ECoul values, indicating strong binding affinity and the ability to form more hydrogen bonds and Vdw interactions with Erl. In contrast, HPB displayed the lowest van der Waals and Coulomb interactions with Erl. Moreover, the HPB: Erl IC system demonstrated superior vdW and Coulomb interactions in Erl-Solvent, while the GCD: Erl complex exhibited the lowest overall Erl-SOL interactions.