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Related Concept Videos

Conserved Binding Sites01:49

Conserved Binding Sites

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 analyses the...
Conserved Binding Sites01:49

Conserved Binding Sites

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 analyses the...
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

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 form...
Conservation of Protein Domains02:26

Conservation of Protein Domains

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 form...
Protein-protein Interfaces02:04

Protein-protein Interfaces

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 polypeptide...
Multi-species Conserved Sequences02:51

Multi-species Conserved Sequences

Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale  studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...

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Related Experiment Video

Updated: Jun 13, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

Consensus protein design without phylogenetic bias.

Christian Jäckel1, Jesse D Bloom, Peter Kast

  • 1Laboratory of Organic Chemistry, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.

Journal of Molecular Biology
|May 4, 2010
PubMed
Summary
This summary is machine-generated.

Randomizing single proteins offers a phylogenetic bias-free alternative for protein stabilization. This method yields active enzymes that are more stable and easier to produce than those from traditional consensus design.

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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
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Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
05:08

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Published on: July 8, 2025

Area of Science:

  • Protein Engineering
  • Biochemistry
  • Molecular Biology

Background:

  • Consensus design stabilizes proteins by leveraging amino acid conservation in homologous sequences.
  • The success of consensus design is contingent upon the phylogenetic diversity of the available sequence data.
  • Phylogenetic bias can limit the effectiveness of traditional protein stabilization strategies.

Purpose of the Study:

  • To explore protein randomization as an alternative to consensus design for protein stabilization.
  • To assess the feasibility of using randomized protein libraries for enzyme engineering.
  • To determine if randomized sequences can yield improved protein stability and production.

Main Methods:

  • Generating binary-patterned libraries through randomization of a single protein.
  • Selecting functional protein sequences from these libraries.
  • Applying consensus design principles to the selected randomized sequences.
  • Characterizing the stability and catalytic activity of the designed enzymes.

Main Results:

  • A small number of functional sequences from randomized libraries enabled consensus design of active enzymes.
  • The designed enzymes exhibited enhanced stability and improved ease of production compared to the starting sequences.
  • Randomization provided sequence diversity largely free from phylogenetic bias.
  • Correlation between catalytic activity and sequence conservation was less consistent in extensively randomized proteins.

Conclusions:

  • Protein randomization is a viable and effective strategy for protein stabilization, offering an alternative to traditional consensus design.
  • This approach can generate highly stable and producible enzymes, overcoming limitations of phylogenetic diversity.
  • Future strategies may involve less extreme mutagenesis to balance stability enhancement with maintained catalytic function.