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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...
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...
Protein-Drug Binding: Determination Methods01:22

Protein-Drug Binding: Determination Methods

Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
Protein-Drug Binding: Mechanism and Kinetics01:16

Protein-Drug Binding: Mechanism and Kinetics

Protein-drug binding refers to the interaction between drugs and proteins within the body. This binding process can occur intracellularly, involving drug interactions with enzymes or receptors within cells, or extracellularly, involving plasma proteins in the blood.
Various forces drive these interactions, including hydrogen bonds, hydrophobic interactions, ionic bonds, electrostatic interactions, and van der Waals forces. These bonds enable drugs to bind to specific sites on proteins,...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...

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Related Experiment Video

Updated: May 31, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

Predicting binding to p-glycoprotein by flexible receptor docking.

Elena Dolghih1, Clifford Bryant, Adam R Renslo

  • 1Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA. lena.dolgikh@ucsf.edu

Plos Computational Biology
|July 7, 2011
PubMed
Summary

P-glycoprotein (P-gp) efflux pump activity can be predicted using a new flexible docking algorithm. This method identifies P-gp substrates based on ligand physicochemical properties rather than specific binding sites.

Related Experiment Videos

Last Updated: May 31, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

Area of Science:

  • Biochemistry
  • Pharmacology
  • Structural Biology

Background:

  • P-glycoprotein (P-gp) is an ATP-dependent efflux pump crucial for xenobiotic transport and drug absorption.
  • Overexpression of P-gp in cancer cells contributes to multidrug resistance.
  • The mouse P-gp crystal structure reveals a large binding cavity supporting an induced-fit ligand binding model.

Purpose of the Study:

  • To develop a novel prediction algorithm for P-gp binding specificity using flexible receptor docking.
  • To assess the algorithm's ability to differentiate P-gp binders from non-binders.
  • To predict potential P-gp substrates, including cellular metabolites.

Main Methods:

  • Employed flexible receptor docking to create a new prediction algorithm.
  • Validated the algorithm using experimental data from P-gp efflux and calcein-inhibition assays.
  • Conducted a blind test on peptidic cysteine protease inhibitors.

Main Results:

  • The algorithm successfully differentiated between P-gp binders and non-binders.
  • The blind test confirmed the model's ability to predict P-gp substrates.
  • Many P-gp substrates appear to bind deeper within the cavity than previously suggested.

Conclusions:

  • P-gp binding specificity is better explained by ligand physicochemical properties and binding site interactions.
  • The developed algorithm offers a valuable tool for predicting P-gp substrates.
  • This research advances our understanding of P-gp function and its role in drug resistance and transport.