AI/ML Assisted De Novo Design Of Hsp90 Inhibitors

Machine learning aided de novo design identifies novel Benzimidazolone based inhibitor-modulators for Heat Shock Protein 90 (HSP90)

Our research began with a machine learning-assisted de novo design process, employing REINVENT4 to design and generate novel molecular structures inspired by known HSP90 inhibitors. The generated molecules underwent a series of rigorous cheminformatics analyses to assess their pharmacokinetic properties. We then evaluated their binding affinities through docking simulations and predicted their absolute binding affinity using the KDeep tool, thereby refining the designed chemical space. From our comprehensive analyses, three benzimidazole-based drug-like candidates emerged as promising HSP90 inhibitors: IM1, IM2, and IM3. Their docking-based binding affinities were impressive, registering at -11.30, -11.50, and -11.20 kcal/mol, respectively. Published article “Machine learning aided de novo design identifies novel Benzimidazolone based inhibitor-modulators for Heat Shock Protein 90 (HSP90)” found in Chemistry Select.