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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...

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...

Protein-Protein Interfaces

Protein-Protein Interfaces

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...

Protein and Protein Structures

Protein and Protein Structures

Conservation of Protein Domains

Conservation of Protein Domains

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Related Experiment Video

Updated: Jan 15, 2026

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

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Published on: July 25, 2013

GeoEvoBuilder: A deep learning framework for efficient functional and thermostable protein design.

Jiale Liu^1,2, Hantian You³, Zheng Guo¹

¹Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.

Proceedings of the National Academy of Sciences of the United States of America

|October 10, 2025

Summary

GeoEvoBuilder, a deep learning framework, directly designs protein sequences with enhanced activity and stability by integrating structural and evolutionary data. This advanced method accelerates protein engineering, bypassing labor-intensive cycles.

Keywords:

catalytic efficiency deep learning functional protein design sequence novelty thermal stability

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

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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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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

Area of Science:

Biochemistry
Computational Biology
Protein Engineering

Background:

Protein engineering traditionally relies on iterative computational design and experimental validation, which is time-consuming.
Existing deep learning methods have advanced protein design but struggle to directly generate sequences with desired properties like high activity and stability.

Purpose of the Study:

To present GeoEvoBuilder, a novel deep learning framework for direct protein sequence design.
To integrate structural and evolutionary constraints adaptively for improved protein engineering outcomes.

Main Methods:

Developed GeoEvoBuilder, a deep learning framework integrating structural and evolutionary information.
Applied GeoEvoBuilder to redesign green fluorescent protein, glutathione peroxidase 4 (GPX4), and dihydrofolate reductase (DHFR).
Validated designed protein structures and functions through experimental methods, including crystal structure determination.

Main Results:

GeoEvoBuilder accurately predicted functional sites and generated stable, active protein sequences.
Redesigned DHFR showed a 20-fold increase in catalytic efficiency and 10 °C higher thermal stability.
Designed proteins exhibited correct structures, with GPX4 variants offering insights into residue dynamic correlations and enzymatic activity regulation.

Conclusions:

GeoEvoBuilder offers a transformative approach to protein engineering by enabling direct sequence design with significant improvements in activity and stability.
The framework successfully redesigned multiple proteins, demonstrating its versatility and potential for exploring vast sequence spaces with substantial residue modifications.
GeoEvoBuilder facilitates a deeper understanding of protein sequence-structure-function-evolution relationships and is publicly available for research.