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Protein Folding

Protein Folding

Protein Denaturation

Protein Denaturation

The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. Folding of the polypeptide chain takes place under specific conditions that energetically favor the folded conformation. In contrast, protein denaturation occurs spontaneously under unfavorable conditions that disrupt the integrity of the folded conformation. Thus, the chemical and physical environment of a protein, such as significant changes in pH...

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...

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Intrinsically Disordered Proteins

Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...

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.
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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.
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Related Experiment Video

Updated: Jul 16, 2025

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

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

Published on: July 14, 2015

A probabilistic view of protein stability, conformational specificity, and design.

Jacob A Stern¹, Tyler J Free², Kimberlee L Stern³

¹Department of Computer Science, Brigham Young University, Provo, UT, USA.

Scientific Reports

|September 19, 2023

Summary

This study introduces BayesDesign, a novel algorithm for protein sequence design that optimizes protein stability and specificity. It outperforms existing methods in enhancing protein properties, offering a new approach to inverse folding.

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Last Updated: Jul 16, 2025

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

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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

Area of Science:

Computational biology
Protein engineering
Machine learning for protein design

Background:

Neural networks are used as probabilistic models for protein sequence design.
Existing inverse folding models use various objective functions with unassessed trade-offs.

Purpose of the Study:

To introduce probabilistic definitions of protein stability and conformational specificity.
To demonstrate the link between these properties and the Boltzmann probability objective.
To propose and evaluate a novel sequence decoding algorithm, BayesDesign.

Main Methods:

Probabilistic definitions of protein stability and conformational specificity were developed.
The relationship between these properties and the Boltzmann probability objective was demonstrated.
A novel algorithm, BayesDesign, was proposed, utilizing Bayes' Rule to maximize the Boltzmann probability objective.

Main Results:

BayesDesign successfully links the Boltzmann probability objective to experimentally verifiable outcomes.
Both BayesDesign and ProteinMPNN enhanced the thermostability of the NanoLuc enzyme.
Both algorithms increased the conformational specificity of the WW structural motif.

Conclusions:

BayesDesign offers a new, effective approach to inverse folding by optimizing the Boltzmann probability objective.
The study validates the link between probabilistic definitions and experimental outcomes in protein design.
Further analysis of potential model error sources is provided.