Related Experiment Video

Updated: Mar 14, 2026

Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
06:27

Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy

Published on: November 30, 2018

9.9K

Molecular dynamics-based analyses of the structural instability and secondary structure of the fibrinogen gamma chain

Shabana Kouser Ali1, P Sneha1, J Priyadharshini Christy1

  • 1a Department of Integrative Biology, School of Biosciences and Technology , VIT University , Vellore , Tamil Nadu 632014 , India.

Journal of Biomolecular Structure & Dynamics
|September 29, 2016
PubMed

Insights

The fibrinogen gamma chain (FGG) D356V mutation impairs protein function by causing structural unfolding. This FGG gene mutation may contribute to blood clotting disorders like dysfibrinogenemia.

Area of Science:

  • Genetics and Molecular Biology
  • Biochemistry
  • Computational Biology

Background:

  • Mutations in the fibrinogen gamma chain (FGG) gene are linked to bleeding and clotting disorders.
  • The FGG Milano I mutation (γ Asp to Val at position 330) is known to impair fibrin polymerization.
  • The D356V (D330V) mutation is predicted to be deleterious, affecting protein function.

Purpose of the Study:

  • To investigate the structural and functional consequences of the D356V (D330V) mutation in the FGG gene.
  • To predict the pathogenicity of the D356V mutation using in silico methods.
  • To understand how this mutation affects fibrin polymerization.

Main Methods:

  • In silico pathogenicity prediction using SIFT, PolyPhen 2, I-Mutant 3.0, Align GV-GD, PhD-SNP, and SNPs&GO.
  • 50-ns molecular dynamics simulation to analyze protein structure and dynamics.
  • Analysis of secondary structure changes and helical region stability.

Main Results:

  • In silico tools predicted the D356V mutation as highly deleterious.
  • Molecular dynamics simulations revealed secondary structure unwinding in the mutant protein within 50 ns.
  • A structural change in the alpha-helical region (residues 352-356) and local transient unfolding were observed.

Conclusions:

  • The D356V mutation leads to conformational changes, including protein unfolding.
  • These structural alterations likely contribute to defective fibrin polymerization.
  • The study provides insights into the molecular mechanisms underlying FGG-related disorders.
Keywords:
D356V (D330V)FGGmolecular simulationsecondary structuresingle nucleotide polymorphism

More Related Videos

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

9.4K
Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States07:09

Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States

Published on: April 1, 2015

12.1K

Related Concept Videos

Protein Folding01:22

Protein Folding

Overview
129.8K
Clot Retraction and Fibrinolysis01:16

Clot Retraction and Fibrinolysis

After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
9.9K
Globular and Fibrous Proteins02:21

Globular and Fibrous Proteins

Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
48.2K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.8K
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
12.6K