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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
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Molecular Chaperones and Protein Folding03:00

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The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
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Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

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ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
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Conservation of Protein Domains Over Different Proteins02:26

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Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
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Protein and Protein Structure02:15

Protein and Protein Structure

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Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
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Amyloid Fibrils03:03

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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. 
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Updated: Aug 30, 2025

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

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Assessing and enhancing foldability in designed proteins.

Dina Listov1, Rosalie Lipsh-Sokolik1, Stéphane Rosset2

  • 1Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.

Protein Science : a Publication of the Protein Society
|August 30, 2022
PubMed
Summary
This summary is machine-generated.

Protein design struggles with low success rates due to misfolding. New computational methods identify and fix suboptimal regions, significantly boosting enzyme efficiency and protein stability for better functional protein design.

Keywords:
AlphaFoldFuncLibRosettacomputational designpSUFERprotein foldingprotein stability

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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
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Area of Science:

  • Protein engineering
  • Computational biology
  • Biochemistry

Background:

  • Modern protein design methods generate numerous proteins but face low success rates for functional proteins.
  • A key challenge in protein design is misfolding and inaccuracies compared to the intended structure.

Purpose of the Study:

  • To develop and apply computational methods for diagnosing and improving suboptimal regions in designed proteins.
  • To enhance the success rate of de novo protein design, particularly for enzymes and stable proteins.

Main Methods:

  • Utilized Rosetta atomistic computational mutation scanning to identify energetically suboptimal positions.
  • Employed AlphaFold2 ab initio structure prediction to detect potential misfolding regions.
  • Applied FuncLib design calculations to optimize identified suboptimal regions in existing protein designs.

Main Results:

  • A previously designed low-efficiency enzyme showed a 330-fold increase in catalytic efficiency after optimization.
  • A de novo designed protein with limited stability demonstrated markedly improved stability and expressibility.
  • Computational methods successfully diagnosed and ameliorated issues in designed proteins, leading to enhanced functionality.

Conclusions:

  • Foldability analysis and targeted computational enhancement are crucial for increasing the success rate of functional protein design.
  • Integrating computational prediction and design optimization can overcome key limitations in current protein engineering approaches.