Molecular Docking Simulations to Identify Ubiquitin Carboxyl-Terminal Hydrolase Isozyme L1 (UCLH1) Biomarker and Therapeutic Target for Aggressive Neuroendocrine Carcinomas

Abstract: Neuroendocrine carcinoma is a rare and aggressive form of cancer that affects the endocrine (hormones) and nervous systems, with a 5-year survival rate of only 39%. Detecting and treating neuroendocrine carcinoma is difficult due to late diagnosis, tumor heterogeneity, and limited effective therapies. UCHL1 is a novel protein found to be elevated in the tissue and plasma of affected NEC patients and can be used as a potential biomarker and therapeutic target. In our work, we have utilized molecular docking simulations to predict inhibitors that can bind to the UCHL1 protein and be used in the diagnosis and treatment of neuroendocrine carcinomas. We hypothesized that ligands will effectively bind to the binding site of the UCHL1 protein. We then used various software to create the UCHL1 protein structure, identify potential ligands, and perform molecular docking simulations. The Alphafold 3 software was used to represent the UCHL1 protein structure visually using its amino acid sequence. The ScanNet software identified the potential binding site. 1092 chemical compounds were scanned and then docked on the UCHL1 binding site using the Autodock Vina software. The results of the molecular docking simulations identified five ligands with the highest binding potential with the UCHL1 binding site. The pharmaceutical properties and binding energy calculations indicate high gastrointestinal absorption, binding potential, and drug likeness. This current work will help develop a novel diagnostic agent for Neuroendocrine carcinoma and pave the way for many potential new treatment methods against the disease.