ArticlePloS one2019
In silico analysis of the V66M variant of human BDNF in psychiatric disorders: An approach to precision medicine.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Exploring alternative approaches to precision medicine through genomics and artificial intelligence - a systematic review.Frontiers in medicine · 2023Pooled it
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- Computational exploration of aphrodisiac potential: identifying inhibitors fromIn silico pharmacology · 2025Article
- An In Silico Analysis of Genetic Variants and Structural Modeling of the Human Frataxin Protein in Friedreich's Ataxia.International journal of molecular sciences · 2024Article
- In silico analysis of the Val66Met mutation in BDNF protein: implications for psychological stress.AMB Express · 2024Article
- Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis.AMB Express · 2023Article
- In Silico Analyses of a Promising Drug Candidate for the Treatment of Amyotrophic Lateral Sclerosis Targeting Superoxide Dismutase I Protein.Pharmaceutics · 2023Article
- Untangling the Conformational Plasticity of V66M Human proBDNF Polymorphism as a Modifier of Psychiatric Disorder Susceptibility.International journal of molecular sciences · 2022Article
- Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs.Memorias do Instituto Oswaldo Cruz · 2022Article
- Mutations of SARS-CoV-2 RBD May Alter Its Molecular Structure to Improve Its Infection Efficiency.Biomolecules · 2021Article
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- In silico analysis of a novel causative mutation in Cadherin23 gene identified in an Omani family with hearing loss.Journal, genetic engineering & biotechnology · 2020Article
- In silico analysis of the tryptophan hydroxylase 2 (TPH2) protein variants related to psychiatric disorders.PloS one · 2020Article
- High-Throughput Screening and Quantum Mechanics for Identifying Potent Inhibitors Against Mac1 Domain of SARS-CoV-2 Nsp3.IEEE/ACM transactions on computational biology and bioinformaticsArticle
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain-derived neurotrophic factor (BDNF) plays an important role in neurogenesis and synapse formation. The V66M is the most prevalent BDNF mutation in humans and impairs the function and distribution of BDNF. This mutation is related to several psychiatric disorders. The pro-region of BDNF, particularly position 66 and its adjacent residues, are determinant for the intracellular sorting and activity-dependent secretion of BDNF. However, it has not yet been fully elucidated. The present study aims to analyze the effects of the V66M mutation on BDNF structure and function. Here, we applied nine algorithms, including SIFT and PolyPhen-2, for functional and stability prediction of the V66M mutation. The complete theoretical model of BNDF was generated by Rosetta and validated by PROCHECK, RAMPAGE, ProSa, QMEAN and Verify-3D algorithms. Structural alignment was performed using TM-align. Phylogenetic analysis was performed using the ConSurf server. Molecular dynamics (MD) simulations were performed and analyzed using the GROMACS 2018.2 package. The V66M mutation was predicted as deleterious by PolyPhen-2 and SIFT in addition to being predicted as destabilizing by I-Mutant. According to SNPeffect, the V66M mutation does not affect protein aggregation, amyloid propensity, and chaperone binding. The complete theoretical structure of BDNF proved to be a reliable model. Phylogenetic analysis indicated that the V66M mutation of BDNF occurs at a non-conserved position of the protein. MD analyses indicated that the V66M mutation does not affect the BDNF flexibility and surface-to-volume ratio, but affects the BDNF essential motions, hydrogen-bonding and secondary structure particularly at its pre and pro-domain, which are crucial for its activity and distribution. Thus, considering that these parameters are determinant for protein interactions and, consequently, protein function; the alterations observed throughout the MD analyses may be related to the functional impairment of BDNF upon V66M mutation, as well as its involvement in psychiatric disorders.
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