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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...
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,...
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...

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Related Experiment Video

Updated: May 30, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Assessing helical protein interfaces for inhibitor design.

Brooke N Bullock1, Andrea L Jochim, Paramjit S Arora

  • 1Department of Chemistry, New York University, New York, New York 10003, USA.

Journal of the American Chemical Society
|August 18, 2011
PubMed
Summary

This study analyzes helical protein interfaces to guide the design of synthetic inhibitors for protein-protein interactions (PPIs). Findings aid in developing novel therapeutics by understanding helix-mediated complex formation.

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Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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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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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

Area of Science:

  • Structural biology
  • Medicinal chemistry
  • Computational biology

Background:

  • Protein-protein interactions (PPIs) mediated by alpha-helices are crucial in biological processes.
  • Designing synthetic inhibitors for these interactions remains challenging due to limited understanding of interface dynamics.
  • Existing helix mimetics have not been widely adopted in biological applications.

Purpose of the Study:

  • To systematically analyze helical protein interfaces in the Protein Data Bank.
  • To provide a comprehensive overview of how helices mediate protein complex formation.
  • To guide the rational design of novel synthetic inhibitors targeting PPIs.

Main Methods:

  • Analysis of the complete dataset of helical protein interfaces from the Protein Data Bank (PDB).
  • Identification of key features and interaction patterns of helices involved in complex formation.
  • Experimental evaluation of newly identified protein complex classes.

Main Results:

  • Characterization of diverse helical interface architectures and interaction modes.
  • Identification of druggable pockets and design strategies for helix-mimicking inhibitors.
  • Validation of computational findings through experimental assessment of novel complexes.

Conclusions:

  • The systematic analysis of helical interfaces provides crucial insights for structure-based drug design.
  • This work bridges the gap between helix mimetic design and their biological application.
  • The findings facilitate the development of targeted synthetic inhibitors for various PPIs.