Analyzing the Effect of V66M Mutation in BDNF in Causing Mood Disorders: A Computational Approach

Mental disorders or mood disorders are prevalent globally irrespective of region, race, and ethnic groups. Of the types of mood disorders, major depressive disorder (MDD) and bipolar disorder (BPD) are the most prevalent forms of psychiatric condition. A number of preclinical studies emphasize the essential role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of mood disorders. Additionally, BDNF is the most common growth factor in the central nervous system along with their essential role during the neural development and the synaptic elasticity. A malfunctioning of this protein is associated with many types of mood disorders. The variant methionine replaces valine at 66th position is strongly related to BPD, and an individual with a homozygous condition of this allele is at a greater risk of developing MDD. There are very sparse reports suggesting the structural changes of the protein occurring upon the mutation. Consequently, in this study, we applied a computational pipeline to understand the effects caused by the mutation on the protein's structure and function. With the use of in silico tools and computational macroscopic methods, we identified a decrease in the alpha-helix nature, and an overall increase in the random coils that could have probably resulted in deformation of the protein.