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Related Concept Videos

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...
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 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...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
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,...

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Related Experiment Video

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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

INTREPID--INformation-theoretic TREe traversal for Protein functional site IDentification.

Sriram Sankararaman1, Kimmen Sjölander

  • 1Department of Electrical Engineering & Computer Science and Department of Bioengineering, University of California, Berkeley, USA. sriram_s@cs.berkeley.edu

Bioinformatics (Oxford, England)
|September 9, 2008
PubMed
Summary

INTREPID, an information-theoretic method, accurately identifies functionally important protein residues using only sequence data. This approach improves predictions of catalytic and specificity-determining residues, outperforming existing methods.

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A Protocol for Computer-Based Protein Structure and Function Prediction
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A Protocol for Computer-Based Protein Structure and Function Prediction

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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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A Protocol for Computer-Based Protein Structure and Function Prediction
16:41

A Protocol for Computer-Based Protein Structure and Function Prediction

Published on: November 3, 2011

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Molecular Biology

Background:

  • Identifying functionally important protein residues is crucial for biological discovery.
  • Existing methods often rely on 3D structural information, which is not universally available.
  • INTREPID offers a sequence-only approach for functional site identification.

Purpose of the Study:

  • To present INTREPID, an information-theoretic method for functional site identification using multiple sequence alignments (MSAs).
  • To evaluate INTREPID's performance in predicting catalytic residues and specificity determinants.
  • To assess the impact of evolutionary divergence on INTREPID's accuracy.

Main Methods:

  • INTREPID utilizes an information-theoretic approach based on Jensen-Shannon divergence to calculate positional conservation scores.
  • It employs a phylogenetic traversal combined with positional conservation scores to rank residues within MSAs.
  • A variant, INTREPID-SPEC, was developed for predicting specificity determinants using subtype information.

Main Results:

  • INTREPID significantly improves catalytic residue prediction accuracy compared to Evolutionary Trace and ConSurf, especially for non-globally conserved positions.
  • The method demonstrates enhanced sensitivity at high specificity values.
  • INTREPID effectively leverages sequence diversity in protein families, with accuracy increasing when including highly divergent homologs.
  • INTREPID-SPEC achieves competitive accuracy in specificity determinant prediction when subtype information is available.

Conclusions:

  • INTREPID provides a robust, sequence-based method for identifying functionally important protein residues.
  • The approach offers significant advantages over existing methods, particularly for proteins lacking structural data.
  • INTREPID is publicly available through the PhyloFacts resource, facilitating broader application in biological research.