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Related Concept Videos

What are Proteins?01:28

What are Proteins?

Proteins are polymers of amino acids linked together by peptide bonds. Proteins and polypeptides are interchangeably used to refer to long chains of amino acids. However, polypeptides have a molecular weight of fewer than 10,000 daltons, while proteins have greater molecular weight.  Polypeptides with less than 20 amino acids are called oligopeptides or simply peptides. Interactions among the constituent amino acid side chains of proteins help them fold into a stable 3-dimensional structure...
What are Proteins?01:55

What are Proteins?

Overview
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...
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...
Amino acids03:42

Amino acids

Amino acids are the monomers that comprise proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. There are 20 common amino acids present in proteins, each with a different R group. Variation in the amino acid sequence is responsible for...
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...

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Related Experiment Video

Updated: Jul 4, 2026

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
06:50

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Published on: January 26, 2024

Computed protonation properties: unique capabilities for protein functional site prediction.

Leonel F Murga1, Ying Wei, Mary Jo Ondrechen

  • 1Department of Chemistry & Chemical Biology and Institute for Complex Scientific Software, Northeastern University, Boston, MA 02115, USA. leonel@brandeis.edu

Genome Informatics. International Conference on Genome Informatics
|June 12, 2008
PubMed
Summary

This study introduces Theoretical Microscopic Titration Curves (THEMATICS) to predict protein functional sites using 3D structures. THEMATICS accurately identify catalytic residues, outperforming other structure-based methods, especially for proteins lacking sequence similarity.

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Area of Science:

  • Computational Biology
  • Structural Bioinformatics
  • Biochemistry

Background:

  • Predicting protein functional sites from 3D structure is crucial for understanding protein function, especially for novel proteins and orphan sequences.
  • Existing methods often rely on sequence or structural similarity, limiting their effectiveness for proteins with unknown homologs or unique folds.

Purpose of the Study:

  • To demonstrate the utility of computed protonation properties for predicting protein catalytic and small molecule recognition sites directly from 3D structure.
  • To introduce and validate the Theoretical Microscopic Titration Curves (THEMATICS) method for this prediction task.

Main Methods:

  • Computed protonation properties of ionizable residues using the calculated electrical potential function from protein 3D structures.
  • Analyzed the shapes of Theoretical Microscopic Titration Curves (THEMATICS) to identify key residues.
  • Validated the method against 169 annotated enzymes in the Catalytic Site Atlas (CSA).

Main Results:

  • THEMATICS accurately predict catalytic sites with high sensitivity and precision, outperforming other 3D-structure-based methods.
  • Performance remains competitive with sequence and structure alignment methods for well-characterized enzymes.
  • Crucially, THEMATICS performance does not degrade for proteins lacking sequence or structural similarity, unlike alignment-based approaches.
  • The method is effective even for open, unbound structures with potential conformational changes upon ligand binding.

Conclusions:

  • Computed protonation properties, specifically THEMATICS, offer a powerful and unique approach for predicting protein functional sites from 3D structure alone.
  • THEMATICS provide a robust alternative to sequence and structure-based methods, particularly valuable for novel proteins and orphan sequences.
  • This method enhances the functional annotation capabilities in structural genomics and drug discovery efforts.