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Related Concept Videos

Protein Folding01:25

Protein Folding

8.4K
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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Ligand Binding Sites02:40

Ligand Binding Sites

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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
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Conserved Binding Sites01:49

Conserved Binding Sites

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Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
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Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

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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-protein Interfaces02:04

Protein-protein Interfaces

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Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
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Updated: Sep 3, 2025

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
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Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid

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Solubility-Aware Protein Binding Peptide Design Using AlphaFold.

Takatsugu Kosugi1, Masahito Ohue1

  • 1Department of Computer Science, School of Computing, Tokyo Institute of Technology, G3-56-4259 Nagatsutacho, Midori-ku, Yokohama City 226-8501, Kanagawa, Japan.

Biomedicines
|July 27, 2022
PubMed
Summary
This summary is machine-generated.

Designing peptides to target protein-protein interactions (PPIs) is challenging. Researchers developed a new computational method using AlphaFold to design soluble peptides with high binding affinity for PPI targets.

Keywords:
AfDesignAlphaFoldpeptide designsolubility

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Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
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Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
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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

Published on: July 25, 2013

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Area of Science:

  • Computational biology
  • Protein engineering
  • Drug discovery

Background:

  • Protein-protein interactions (PPIs) are crucial biological processes but difficult to target with small molecules.
  • Peptides offer a promising alternative for targeting PPIs, yet computational design of effective peptide sequences remains a challenge.
  • Recent advances in protein structure prediction, such as AlphaFold, enable de novo protein design.

Purpose of the Study:

  • To develop a computational method for designing peptides that can target protein-protein interaction (PPI) interfaces.
  • To address the challenge of low peptide solubility often encountered in de novo peptide design.
  • To enhance the affinity and solubility of designed peptides for potential therapeutic applications.

Main Methods:

  • Utilized the AfDesign 'binder hallucination' protocol, leveraging AlphaFold for de novo peptide design targeting PPIs.
  • Developed a novel solubility loss function incorporating amino acid solubility indices.
  • Integrated the solubility loss function into the AfDesign protocol to create a solubility-aware design method.

Main Results:

  • Peptide sequences designed with the solubility-aware protocol exhibited improved solubility, correlating with the weight of the solubility loss function.
  • Designed peptides demonstrated characteristics aligned with amino acid solubility indices.
  • Sequences generated by the new protocol showed higher predicted binding affinity compared to random or single-residue substitution sequences.

Conclusions:

  • The developed solubility-aware AfDesign protocol enables the computational design of peptides targeting PPI interfaces with controlled solubility.
  • This approach enhances the feasibility of using peptides as therapeutic agents against challenging PPI targets.
  • The method offers a significant advancement in de novo peptide design for drug discovery.