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Related Concept Videos

Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Protein Folding01:22

Protein Folding

Overview
Protein Folding01:25

Protein Folding

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...
Protein Folding01:22

Protein Folding

Overview

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Updated: Jun 23, 2026

Modeling an Enzyme Active Site using Molecular Visualization Freeware
14:37

Modeling an Enzyme Active Site using Molecular Visualization Freeware

Published on: December 25, 2021

Closing the side-chain gap in protein loop modeling.

Karen A Rossi1, Akbar Nayeem, Carolyn A Weigelt

  • 1Bristol-Myers Squibb Company, Research & Development, Computer-Assisted Drug Design, P.O. Box 5400, Princeton, NJ 08543, USA. karen.rossi@bms.com

Journal of Computer-Aided Molecular Design
|May 22, 2009
PubMed
Summary
This summary is machine-generated.

Accurate protein loop modeling is crucial for structure-based drug design. This study shows re-sampling side-chains improves loop models, making them suitable for drug discovery applications.

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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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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:

  • Computational biology
  • Structural biology
  • Drug discovery

Background:

  • Accurate protein modeling is essential for structure-based drug design.
  • Protein loops present a significant challenge in modeling and refinement.
  • Inaccurate loop modeling, particularly side-chain orientation, can hinder ligand docking.

Purpose of the Study:

  • To evaluate the impact of side-chain re-sampling on modeled loop conformations.
  • To assess the accuracy of side-chain modeling in protein loops.
  • To determine the suitability of modeled loops for structure-based drug design.

Main Methods:

  • Generation of loop conformations.
  • Re-sampling of side-chains using various algorithms.
  • Evaluation of backbone and side-chain conformations against native structures.
  • Comparison of rotamer libraries, systematic torsion scans, and knowledge-based methods.

Main Results:

  • Modeled loops can achieve high-quality backbone conformations.
  • Side-chain orientations in modeled loops are often inaccurate.
  • Side-chain re-sampling significantly improves loop model quality.
  • Commercial algorithms demonstrate varying abilities in accurate side-chain modeling.

Conclusions:

  • Accurate side-chain modeling is critical for reliable protein loop representation.
  • Side-chain re-sampling strategies enhance the utility of modeled loops for drug design.
  • Further development of side-chain modeling algorithms is needed for optimal structure-based design.