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Related Concept Videos

Protein Folding01:25

Protein Folding

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Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
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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,...
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Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast
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Advanced computational approaches to understand protein aggregation.

Deepshikha Ghosh1, Anushka Biswas2, Mithun Radhakrishna

  • 1Department of Biological Sciences and Engineering, Indian Institute of Technology (IIT) Gandhinagar, Palaj, Gujarat 382355, India.

Biophysics Reviews
|April 29, 2024
PubMed
Summary
This summary is machine-generated.

Computational methods and bioinformatics tools are revolutionizing the study of protein aggregation. These techniques offer crucial insights into disease mechanisms and aid in developing therapeutic strategies for conditions like Alzheimer's and Parkinson's.

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Characterizing Individual Protein Aggregates by Infrared Nanospectroscopy and Atomic Force Microscopy
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Area of Science:

  • Molecular Biology
  • Computational Biology
  • Bioinformatics

Background:

  • Protein aggregation is central to neurodegenerative diseases like Alzheimer's and Parkinson's, as well as cataracts.
  • Understanding the complex dynamics of protein aggregation presents significant challenges in molecular biology.
  • Precise predictive tools are essential for deciphering protein aggregation mechanisms.

Purpose of the Study:

  • To review the role of computational methods and bioinformatics in understanding protein aggregation.
  • To highlight the application of molecular simulations in studying aggregation pathways.
  • To explore the integration of computational approaches with experimental data for therapeutic development.

Main Methods:

  • Molecular Dynamics (MD) simulations (atomistic and coarse-grained) including advanced techniques like replica exchange, Metadynamics (MetaD), and umbrella sampling.
  • Markov state modeling for analyzing chaperone mechanisms in cataract formation.
  • Bioinformatics, sequence analysis, structural data analysis, machine learning, and artificial intelligence for predicting aggregation propensity.

Main Results:

  • MD simulations provide microscopic insights into protein interactions and aggregation pathways in diseases.
  • Computational tools are indispensable for predicting aggregation-prone regions and protein aggregation propensity.
  • Advanced computational methods elucidate disease-specific aggregation mechanisms, such as in Alzheimer's and Parkinson's disease.

Conclusions:

  • Computational methods and bioinformatics have catalyzed breakthroughs in understanding protein aggregation.
  • The synergy between computational approaches and empirical data is key to developing therapeutic strategies.
  • This review underscores the impact of computational biology on unraveling the molecular basis of protein aggregation and its clinical implications.