Unveiling the TP5 dual binding mechanism and structure-based search for potential dual inhibitors of tubulin and PD-L1

efficacy, was included as a reference compound, despite lacking structural information about its binding modes. Our simulations provide detailed structural insights into TP5's interactions with both tubulin and PD-L1, revealing its colchicine-site mimicry and moderate stabilization of PD-L1 dimers. Additionally, several newly identified compounds displayed more favorable binding energies than TP5, particularly frag2_571, frag2_3214, frag2_3522, frag2_8390, frag2_8592, and bf_1, which exhibited stable dual-target interactions and similar structural effects to TP5. ADMET predictions supported their pharmacological potential, highlighting them as promising scaffolds for further optimization and experimental evaluation. These findings support the utility of fragment-based and AI-guided design in the discovery of multitarget anticancer agents.