Related Experiment Video
Updated: Jun 6, 2025
10:58
Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
17.0K
Systematic analysis of the relationship between fold-dependent flexibility and artificial intelligence protein
Neshatul Haque1, Jessica B Wagenknecht1, Brian D Ratnasinghe1
1Computational Structural Genomics Unit, Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI, United States of America.
Plos One
|November 26, 2024
Summary
Artificial Intelligence (AI) models like AlphaFold v2 accurately predict a single protein structure. However, many proteins exhibit flexibility, with some folds showing significant conformational variation vital for biological processes.
Area of Science:
- Structural biology
- Computational biology
- Biophysics
Background:
- AI-driven protein structure prediction is revolutionizing scientific discovery.
- Proteins possess modular organization based on archetypal folds.
- The conformational states captured by AI predictions for flexible proteins remain unclear.
Purpose of the Study:
- To investigate whether AI-predicted protein structures represent single conformations or average states.
- To determine if protein fold-dependent conformational heterogeneity exists.
- To analyze the topological rigidity versus heterogeneity of protein folds using experimental data.
Main Methods:
- Analysis of 2878 proteins with multiple experimental structures.
- Comparison of experimental structures against AI-predicted structures (AlphaFold v2).
- Estimation of protein topological rigidity and conformational heterogeneity.
Main Results:
- AlphaFold v2 accurately predicts a single conformation for most protein folds (99.68%).
- A significant percentage of folds (27.70%) exhibit experimental structures deviating over 2.5Å RMSD from AI predictions.
- Protein folds with high conformational heterogeneity are crucial for biological processes like immune regulation and metabolism.
Conclusions:
- AI structure prediction tools like AlphaFold v2 provide highly accurate single conformations but may not capture inherent protein flexibility.
- Understanding protein conformational heterogeneity is critical for interpreting AI-derived structures and advancing biological insights.
- The study highlights the need to integrate protein dynamics into structure prediction databases, bridging the gap between static predictions and functional flexibility.
Related Concept Videos
01:22Protein Folding
117.4K
Overview
117.4K
01:29Protein Folding Quality Check in the RER
3.7K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
01:24Protein Organization
6.2K
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....
The primary structure of a protein is its amino acid sequence....
6.2K
02:26Conservation of Protein Domains Over Different Proteins
10.8K
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...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.8K
02:15Protein and Protein Structure
78.5K
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...
A protein's shape is critical to its function. For example, an enzyme...
78.5K
01:49Conserved 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...
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