Computational profiling of antidepressants-induced molecular docking with placental proteins (IGFBP-1, PlGF-1 and GATA3)

Background. Antidepressants readily penetrate the intrauterine environment, potentially influencing the genetic expression of specific genes in the fetal portion of the placenta. Nevertheless, there is a lack of understanding regarding the precise impact of these medications on placental proteins, which play critical roles in embryonic development. Methods. Therefore, investigating their interaction with placental proteins is crucial. Utilizing computa­tional analysis and molecular docking software, this study explores the interactions between ten antidepressant medications and the proteins IGFBP-1, PlGF-1, and GATA3 through dynamic simulation. Results. The findings from molecular docking reveal a clear inclination of all drugs to bind with these proteins, albeit with varying degrees of affinity. Certain drugs (Trazodone, Amitriptyline, Nortriptyline, and Mirtazapine) exhibit high affinities for these proteins, while others show lower affinities (Desvenlafaxine, Phenelzine, and Tranylcypromine). The affinity values for IGFBP-1 and PlGF-1 ranged from -6.8 to -3.9 kcal/mol, with an average of -5.9 kcal/mol. In comparison, the affinity range for the GATA3 protein was -7.8 to -5.1 kcal/mol. Conclusion. The molecular dynamics simulation of the four drugs with high affinity to proteins revealed that, except for Trazodone, they did not maintain stability within acceptable limits. Interestingly, Trazodone showed signs of stability with the IGFBP-1 protein throughout the molecular dynamics simulation. These findings may indicate that Trazodone potentially influences embryonic development, raising safety concerns for maternal-fetal health. Choosing the safest antidepressants requires balancing their mental health benefits with their potential molecular effects on placental proteins, ensuring the well-being of both mother and fetus during pregnancy. Further research and clinical guidelines should explore the interplay between antidepressant affinities and maternal-fetal health outcomes for a more informed approach to perinatal mental health care.