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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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Protein Organization01:24

Protein Organization

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Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
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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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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.
A protein's shape is critical to its function. For example, an enzyme...
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Peptide Bonds02:43

Peptide Bonds

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A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...
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Amino acids03:42

Amino acids

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Amino acids are the monomers that comprise proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. There are 20 common amino acids present in proteins, each with a different R group. Variation in the amino acid sequence is responsible...
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Updated: Aug 9, 2025

Capillary Electrophoresis-based Hydrogen/Deuterium Exchange for Conformational Characterization of Proteins with Top-down Mass Spectrometry
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Conformational Analysis of Charged Homo-Polypeptides.

Lavi S Bigman1, Yaakov Levy1

  • 1Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.

Biomolecules
|February 25, 2023
PubMed
Summary

Intrinsically disordered regions (IDRs) in proteins show distinct charged repeat patterns. Molecular dynamics simulations reveal that negatively charged repeats (D/E) are more sensitive to salt concentration than positively charged repeats (K/R).

Keywords:
D/E repeatsK/R repeatsintrinsically disordered proteinsmolecular dynamics simulationspolyelectrolytes

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Area of Science:

  • Biophysics
  • Computational Biology
  • Protein Science

Background:

  • Proteins contain intrinsically disordered regions (IDRs) with charged residues.
  • IDRs exhibit polyampholytic or polyelectrolytic characteristics.
  • Polyelectrolytic IDRs include Lys/Arg (K/R) or Asp/Glu (D/E) repeats, with D/E repeats being longer and more common in eukaryotes.

Purpose of the Study:

  • To investigate the conformational ensemble of charged homo-polypeptides.
  • To understand the prevalence of D/E repeats over K/R repeats.
  • To explain the higher abundance of Glu (E) and Lys (K) residues in repeats.

Main Methods:

  • Molecular dynamics simulations of charged homo-polypeptides (polyK, polyR, polyD, polyE).
  • Analysis of conformational preferences and dynamics under varying salt concentrations.

Main Results:

  • Conformational preferences and dynamics of polyelectrolytic polypeptides are salt-dependent.
  • PolyD and polyE exhibit greater salt sensitivity than polyK and polyR.
  • PolyD and polyE form more compact conformations due to divalent cation adsorption.

Conclusions:

  • Biophysical factors explain the relative abundance of charged amino acids.
  • The greater abundance of D/E repeats over K/R repeats is attributed to their distinct salt-dependent conformational behavior.