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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-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...

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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
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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.
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Related Experiment Video

Updated: May 30, 2026

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Published on: January 26, 2024

Predicting the tolerated sequences for proteins and protein interfaces using RosettaBackrub flexible backbone design.

Colin A Smith¹, Tanja Kortemme

¹Graduate Program in Biological and Medical Informatics, University of California San Francisco, San Francisco, California, United States of America.

|July 27, 2011

Summary

This study presents a computational method using Rosetta software to predict protein sequences that maintain function. The approach helps characterize protein interactions and design new protein sequences for engineering novel functions.

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Published on: January 26, 2024

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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

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Published on: July 8, 2025

Area of Science:

Computational Biology
Protein Engineering
Molecular Modeling

Background:

Predicting tolerated protein sequences is crucial for understanding protein interaction specificity.
Engineering proteins with novel functions requires robust methods for sequence design.
Existing methods may lack the flexibility to explore diverse conformational states.

Purpose of the Study:

To develop a general computational method for predicting tolerated protein sequences.
To enable the design of sequence libraries for protein engineering.
To characterize protein interaction specificity and stability.

Main Methods:

Utilized Rosetta molecular modeling software for flexible backbone protein design.
Employed Monte Carlo simulations with backrub backbone and side chain moves to generate conformational ensembles.
Applied simulated annealing and genetic algorithm optimization to identify low-energy sequences.
Incorporated reweighting of interactions to emphasize specific functional requirements.

Main Results:

Developed and validated a general method for estimating tolerated sequence space.
Provided detailed protocols, benchmarks, and analyses for the protein design method.
Demonstrated the method's applicability in stabilizing proteins and protein interfaces.

Conclusions:

The presented method offers a versatile approach for predicting and designing protein sequences.
It facilitates the characterization of protein interaction specificity and the engineering of new protein functions.
Potential applications include stabilizing interactions with small molecules, DNA, RNA, and specific protein conformations.