Related Experiment Video
Updated: Jan 31, 2026
07:22
Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
Published on: January 12, 2024
4.5K
Evaluating the effect of BDNF Val66Met polymorphism on complex formation with HAP1 and Sortilin1 via structural
Mozhdeh Zamani1, Mahboobeh Eslami2, Navid Nezafat3
1Colorectal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Computational Biology and Chemistry
|January 3, 2019
Summary
The Val66Met polymorphism in brain-derived neurotrophic factor (BDNF) gene may destabilize proBDNF structure, potentially impacting its secretion and contributing to neurological and eating disorders.
Area of Science:
- Neuroscience
- Structural Bioinformatics
- Molecular Dynamics
Background:
- Brain-derived neurotrophic factor (BDNF) is crucial for neuronal health, appetite, and energy balance.
- The BDNF Val66Met polymorphism (rs6265) is linked to psychiatric, neurodegenerative, and eating disorders.
- Huntingtin-associated protein-1 (HAP1) and sortilin1 regulate proBDNF trafficking and secretion.
Purpose of the Study:
- To investigate the structural impact of the BDNF Val66Met polymorphism on proBDNF.
- To analyze the effect of this polymorphism on proBDNF interactions with HAP1 and sortilin1.
Main Methods:
- Homology modeling, structure validation, and refinement.
- Protein-protein docking.
- Molecular dynamics (MD) simulations to assess complex stability (RMSD, RMSF, Rg).
Main Results:
- Mutant proBDNF (Val66Met) exhibited higher RMSD and RMSF values compared to wild-type.
- The mutant proBDNF showed less stable interactions with HAP1 and sortilin1.
- Variable Radius of Gyration (Rg) in mutant complexes indicated reduced compactness.
Conclusions:
- The Val66Met polymorphism induces structural instability in proBDNF.
- This instability may impair proBDNF secretion, potentially contributing to associated disorders.
- Further experimental validation is needed to confirm these computational findings.
Related Concept Videos
03:45Formation of Complex Ions
26.1K
A type of Lewis acid-base chemistry involves the formation of a complex ion (or a coordination complex) comprising a central atom, typically a transition metal cation, surrounded by ions or molecules called ligands. These ligands can be neutral molecules like H2O or NH3, or ions such as CN− or OH−. Often, the ligands act as Lewis bases, donating a pair of electrons to the central atom. These types of Lewis acid-base reactions are examples of a broad subdiscipline called coordination...
26.1K
01:32Assembly of Complex Microtubule Structures
2.5K
Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
2.5K
01:05Single Nucleotide Polymorphisms-SNPs
18.3K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
18.3K
01:29Self-Evaluation Maintenance Model
303
The Self-Evaluation Maintenance (SEM) model offers a psychological framework to understand how individuals’ self-esteem is influenced by the achievements of others, particularly those with whom they share close personal bonds. The SEM model operates when personal rather than social identity guides individuals. Central to this model is the notion that individuals have an inherent desire to preserve a favorable self-image, which is continuously shaped by interpersonal comparisons and...
303
02:58Crystal Field Theory - Octahedral Complexes
30.8K
Crystal Field Theory
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
30.8K
01:21Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
716
Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
716