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Related Concept Videos

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...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence 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...
Drug Discovery: Overview01:26

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...

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Related Experiment Video

Updated: Jul 15, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Computational approach to site-directed ligand discovery.

Gergely Tóth1, Kiran Mukhyala, James A Wells

  • 1Locus Pharmaceuticals, Blue Bell, Pennsylvania 19422, USA. gergely.toth@gmail.com

Proteins
|April 21, 2007
PubMed
Summary

A new computational method, Systematic Conformational Search & Induced Fit (SCI&FI), predicts protein-ligand binding sites and dynamics. It models induced fit effects, complementing experimental tethering for drug discovery.

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Area of Science:

  • Computational chemistry
  • Structural biology
  • Drug discovery

Background:

  • Site-directed ligand discovery using tethering is crucial for identifying novel drug candidates.
  • Understanding protein-ligand interactions requires accurate prediction of binding sites, modes, and dynamics.
  • Modeling protein conformational changes upon ligand binding (induced fit) is essential for precise drug design.

Purpose of the Study:

  • To present a novel computational approach, Systematic Conformational Search & Induced Fit (SCI&FI), for site-directed ligand discovery.
  • To enable prediction of binding sites, modes, and dynamics of covalently tethered small molecules.
  • To incorporate the modeling of protein induced fit conformational changes due to tether binding.

Main Methods:

  • Systematic Conformational Search & Induced Fit (SCI&FI) computational method.
  • Modeling of small molecule fragments covalently tethered to proteins.
  • Elucidation of potential binding sites and receptor conformational changes.

Main Results:

  • SCI&FI successfully predicts binding site, mode, and dynamics for tethered ligands.
  • The method models induced fit conformational changes in proteins.
  • Initial validation involved predicting structures for Interleukin-2 and Interleukin-4 tethered-protein systems.

Conclusions:

  • SCI&FI offers a comprehensive computational approach to site-directed ligand discovery.
  • The method provides insights into binding preferences and protein conformational adaptability.
  • SCI&FI serves as a valuable computational complement to experimental tethering techniques.