Exploring the blood-testis-barrier dynamics by targeting Laminin-α2: ADMET, molecular docking, and dynamics simulation study.

Laminin-α2 (LAMA2) is a critical regulatory protein of the blood-testis barrier (BTB), essential for preserving its structural and functional integrity. This study aims to decipher the interaction of LAMA2, BTB-regulating protein with melatonin (MLT). As there is no FDA-approved drug for male infertility, clomiphene (CP) was considered an off-market conventional drug for male infertility treatment. Molecular docking of MLT and CP with LAMA2 was performed. Molecular dynamic simulations (MDS) of LAMA2 with MLT revealed the top docked complex and had a binding energy of -88.030 ± 12.687 kJ/mol as compared with CP which had -62.952 ± 9.677 kJ/mol. Additionally, MDS analysis revealed that MLT formed a higher number of H-bonds compared to CP, producing a more compact and stable LAMA-MLT complex. Additionally, SASA, RG, and MM-PBSA binding energies studies confirmed the result. Our in-silico study predicted MLT could be a potential drug candidate for interaction with LAMA2 expressions, thereby maintaining BTB integrity. This study is one of the first reports on the molecular interaction and potential of MLT in targeting LAMA2 that provides an overview of its regulation on significant BTB-regulating proteins.