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Related Concept Videos

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...
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...
Ligand Binding Sites02:40

Ligand Binding Sites

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...
Ligand Binding Sites02:40

Ligand Binding Sites

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...
Protein Networks02:26

Protein Networks

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
Protein Organization01:24

Protein Organization

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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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

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

Published on: July 25, 2013

Computational design of protein-small molecule interfaces.

Brittany Allison1, Steven Combs1, Sam DeLuca2

  • 1Department of Chemistry, 7330 Stevenson Center, Station B 351822, Nashville, TN 37235, USA.

Journal of Structural Biology
|August 22, 2013
PubMed
Summary

Designing proteins to bind small molecules is challenging. Benchmarking Rosetta on 43 complexes showed limited success in predicting binding site sequences, especially with full ligand reorientation.

Keywords:
Computational interface designLigand dockingProtein-small molecule interactionRosettaRosettaLigandSequence optimization

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Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
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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
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Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
06:50

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Published on: January 26, 2024

Area of Science:

  • Protein engineering
  • Computational biology
  • Biochemistry

Background:

  • Designing proteins to bind small molecules is a complex challenge due to limited intermolecular interactions and strict geometric requirements.
  • Interactions range from short-range van der Waals forces for apolar molecules to longer-ranged, environment-dependent forces like hydrogen bonds for polar molecules.

Purpose of the Study:

  • To benchmark the Rosetta computational algorithm for its effectiveness in designing protein-small molecule binding interfaces.
  • To evaluate Rosetta's performance across a diverse set of 43 protein-ligand complexes.

Main Methods:

  • Utilized the Rosetta algorithm to simulate the redesign of protein binding sites for small molecule ligands.
  • Assessed performance by measuring sequence recovery in the binding site under different ligand reorientation conditions (limited vs. full).

Main Results:

  • Achieved average sequence recoveries of 59% (limited reorientation) and 48% (full reorientation) in the binding site.
  • Sequence recovery for key binding residues was 52% (limited) and 27% (full), correlating with ligand displacement.
  • Performance varied based on ligand properties and interaction types.

Conclusions:

  • Rosetta demonstrates moderate success in protein-small molecule interface design, with performance significantly impacted by ligand mobility.
  • Further advancements are needed to improve prediction accuracy, especially for cases allowing full ligand reorientation.
  • The findings highlight the importance of considering ligand flexibility in computational protein design.