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Conserved Binding Sites

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 Organization

Protein Organization

Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.

Gene Evolution - Fast or Slow?

Gene Evolution - Fast or Slow?

The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...

Protein-protein Interfaces

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...

Protein and Protein Structure

Protein and Protein Structure

Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...

Conservation of Protein Domains Over Different Proteins

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...

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

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Integrating sequence variation and protein structure to identify sites under selection.

Austin G Meyer¹, Claus O Wilke

¹Section of Integrative Biology, Institute for Cellular and Molecular Biology, Center for Computational Biology and Bioinformatics, University of Texas at Austin, Austin, TX, USA.

Molecular Biology and Evolution

|September 15, 2012

Summary

We developed a new method to find protein evolution hotspots by integrating 3D structure data with evolutionary models. This approach improves the accuracy of identifying sites under selection pressure.

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Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

Published on: July 16, 2017

Area of Science:

Evolutionary biology
Structural biology
Bioinformatics

Background:

Identifying sites under selection in protein-coding genes is crucial for understanding protein evolution and function.
Traditional models often overlook the impact of protein structure on evolutionary rates.

Purpose of the Study:

To present a novel method for identifying sites under selection by integrating protein 3D structure information, specifically relative solvent accessibility (RSA), with evolutionary models.
To develop an RSA-dependent likelihood model for coding-sequence evolution.
To establish a more accurate neutral baseline for evolutionary rates.

Main Methods:

Developed a random-effects likelihood sites model where evolutionary rate classes are dependent on residue relative solvent accessibility (RSA).
Modeled RSA dependence using linear functions.
Applied the model to influenza hemagglutinin and neuraminidase protein sequences.

Main Results:

The RSA-dependent model significantly outperformed traditional RSA-independent models in fitting molecular sequence data.
The model provides an RSA-dependent neutral baseline for the evolutionary rate ratio (ω = dN/dS).
Applied to influenza proteins, the method identified known functional sites under selection, including positively selected sites near the sialic acid-binding site in hemagglutinin and the oseltamivir resistance site in neuraminidase.

Conclusions:

The novel RSA-dependent model offers a more accurate approach to identifying sites under selection in protein-coding genes.
This method enhances our understanding of evolutionary pressures shaping protein function and can be applied to proteins with available or modeled 3D structures.