Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Ligand Binding Sites02:40

Ligand Binding Sites

12.7K
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...
12.7K
Henderson-Hasselbalch Equation02:48

Henderson-Hasselbalch Equation

68.1K
The ionization-constant expression for a solution of a weak acid can be written as:
68.1K
Acid–Base Equilibria: Activity-Based Definition of pH01:10

Acid–Base Equilibria: Activity-Based Definition of pH

537
For an ideal solution, the pH is defined as the negative logarithm of the hydrogen ion concentration. For a non-ideal solution, an accurate measurement of the pH must consider the negative logarithm of the hydrogen ion activity rather than concentration. In such a solution, the pH can be more accurately defined as the negative logarithm of a product of the hydrogen ion concentration and its activity coefficient.
In solutions of very low ionic strength—for example, pure water—the...
537
Extraction: Effects of pH00:53

Extraction: Effects of pH

428
Consider a neutral form of an amine, B, with a partition coefficient, K, in a liquid mixture containing organic and aqueous phases. The pH of the aqueous phase affects the charge on acidic and basic solutes, and the charged form is usually more soluble in the aqueous phase. Suppose the conjugate acid form of the amine is soluble only in the aqueous phase while the base form is soluble in both phases. Then the distribution coefficient, D, can be given as the ratio of amine concentration in the...
428
Protein Buffers in Blood Plasma and Cells01:20

Protein Buffers in Blood Plasma and Cells

539
The human body utilizes protein buffer systems to maintain a stable pH. These systems capitalize on the dual role of amino acids, which can act as acids or bases by accepting or releasing hydrogen ions in response to pH changes. Protein buffer systems are particularly significant in the extracellular fluid (ECF) and intracellular fluid (ICF) of active cells, where structural and functional proteins provide substantial buffering capacity.
Certain amino acids can exist in a zwitterion state at a...
539
Conserved Binding Sites01:49

Conserved Binding Sites

4.2K
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...
4.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Multifunctional ACE2-nanobody fusion design for pan-specific neutralization and cardiovascular protection in SARS coronavirus infection.

Antimicrobial agents and chemotherapy·2026
Same author

Optimization of synthetic human V<sub>H</sub> affinity and solubility through in vitro affinity maturation and minimal camelization.

Protein science : a publication of the Protein Society·2025
Same author

Sequence-based engineering of pH-sensitive antibodies for tumor targeting or endosomal recycling applications.

mAbs·2024
Same author

A Novel Antigen Design Strategy to Isolate Single-Domain Antibodies that Target Human Nav1.7 and Reduce Pain in Animal Models.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2024
Same author

Enhanced antibody-antigen structure prediction from molecular docking using AlphaFold2.

Scientific reports·2023
Same author

Exploring rigid-backbone protein docking in biologics discovery: a test using the DARPin scaffold.

Frontiers in molecular biosciences·2023

Related Experiment Video

Updated: Jun 1, 2025

Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability
09:49

Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability

Published on: April 2, 2015

10.6K

Improved Structure-Based Histidine pKa Prediction for pH-Responsive Protein Design.

Hervé Hogues1, Wanlei Wei1, Traian Sulea1

  • 1Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Avenue, Montreal, Quebec H4P 2R2, Canada.

Journal of Chemical Information and Modeling
|January 18, 2025
PubMed
Summary
This summary is machine-generated.

This study presents a new computational method for predicting histidine pKa values, achieving 0.4 pH unit accuracy. This tool aids in designing pH-sensitive biomolecules for targeted therapies.

More Related Videos

Determination of the Gas-phase Acidities of Oligopeptides
11:00

Determination of the Gas-phase Acidities of Oligopeptides

Published on: June 24, 2013

11.1K
Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

1.6K

Related Experiment Videos

Last Updated: Jun 1, 2025

Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability
09:49

Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability

Published on: April 2, 2015

10.6K
Determination of the Gas-phase Acidities of Oligopeptides
11:00

Determination of the Gas-phase Acidities of Oligopeptides

Published on: June 24, 2013

11.1K
Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

1.6K

Area of Science:

  • Biochemistry and Molecular Biology
  • Computational Chemistry
  • Structural Biology

Background:

  • Histidine's near-neutral pKa is crucial for engineering pH-sensitive biomolecules, particularly antibodies targeting acidic tumor microenvironments or cellular endosomes.
  • Histidine pKa values exhibit significant variability (up to 4 pH units), influenced by protein interactions, complicating targeted mutations.
  • Accurate pKa prediction is essential for designing novel therapeutic proteins, but current methods lack sufficient precision.

Purpose of the Study:

  • To develop and validate an improved computational method for predicting histidine pKa values in proteins.
  • To enhance the accuracy of pKa predictions beyond the current standard of 1.0 pH unit.
  • To provide a tool that facilitates the rational design of pH-responsive mutations in biomolecules.

Main Methods:

  • Utilized Amber force field electrostatics with a continuum solvent model.
  • Incorporated limited rotameric sampling and proton optimization.
  • Applied an empirical correction for buried side-chains and validated against the PKAD database.

Main Results:

  • Achieved a mean unsigned error of 0.4 pH units for histidine pKa predictions.
  • Evaluated 91 histidines across 38 diverse protein structures.
  • Demonstrated improved accuracy compared to existing prediction standards.

Conclusions:

  • The developed method significantly enhances the accuracy of histidine pKa prediction.
  • This advancement will improve in-silico design of pH-responsive mutations for therapeutic applications.
  • The JustHISpKa software is now available to assist researchers in protein engineering.