Discrete structural features among interface residue-level classes

Gopichandran Sowmya, Shoba Ranganathan

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Protein-protein interaction (PPI) is essential for molecular functions in biological cells. Investigation on protein interfaces of known complexes is an important step towards deciphering the driving forces of PPIs. Each PPI complex is specific, sensitive and selective to binding. Therefore, we have estimated the relative difference in percentage of polar residues between surface and the interface for each complex in a non-redundant heterodimer dataset of 278 complexes to understand the predominant forces driving binding. Results: Our analysis showed ~60% of protein complexes with surface polarity greater than interface polarity (designated as class A). However, a considerable number of complexes (~40%) have interface polarity greater than surface polarity, (designated as class B), with a significantly different p-value of 1.66E-45 from class A. Comprehensive analyses of protein complexes show that interface features such as interface area, interface polarity abundance, solvation free energy gain upon interface formation, binding energy and the percentage of interface charged residue abundance distinguish among class A and class B complexes, while electrostatic visualization maps also help differentiate interface classes among complexes. Conclusions: Class A complexes are classical with abundant non-polar interactions at the interface; however class B complexes have abundant polar interactions at the interface, similar to protein surface characteristics. Five physicochemical interface features analyzed from the protein heterodimer dataset are discriminatory among the interface residue-level classes. These novel observations find application in developing residue-level models for protein-protein binding prediction, protein-protein docking studies and interface inhibitor design as drugs.

LanguageEnglish
Article numberS8
Pages1-8
Number of pages8
JournalBMC Bioinformatics
Volume16
DOIs
Publication statusPublished - 9 Dec 2015

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Proteins
Protein
Polarity
Class
Protein-protein Interaction
Driving Force
Percentage
Drug Design
Solvation
Binding energy
Static Electricity
Protein Binding
Free energy
Electrostatics
Carrier Proteins
Membrane Proteins
Visualization
Docking
Binding Energy
p-Value

Bibliographical note

Copyright the Author(s) 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Cite this

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abstract = "Background: Protein-protein interaction (PPI) is essential for molecular functions in biological cells. Investigation on protein interfaces of known complexes is an important step towards deciphering the driving forces of PPIs. Each PPI complex is specific, sensitive and selective to binding. Therefore, we have estimated the relative difference in percentage of polar residues between surface and the interface for each complex in a non-redundant heterodimer dataset of 278 complexes to understand the predominant forces driving binding. Results: Our analysis showed ~60{\%} of protein complexes with surface polarity greater than interface polarity (designated as class A). However, a considerable number of complexes (~40{\%}) have interface polarity greater than surface polarity, (designated as class B), with a significantly different p-value of 1.66E-45 from class A. Comprehensive analyses of protein complexes show that interface features such as interface area, interface polarity abundance, solvation free energy gain upon interface formation, binding energy and the percentage of interface charged residue abundance distinguish among class A and class B complexes, while electrostatic visualization maps also help differentiate interface classes among complexes. Conclusions: Class A complexes are classical with abundant non-polar interactions at the interface; however class B complexes have abundant polar interactions at the interface, similar to protein surface characteristics. Five physicochemical interface features analyzed from the protein heterodimer dataset are discriminatory among the interface residue-level classes. These novel observations find application in developing residue-level models for protein-protein binding prediction, protein-protein docking studies and interface inhibitor design as drugs.",
author = "Gopichandran Sowmya and Shoba Ranganathan",
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Discrete structural features among interface residue-level classes. / Sowmya, Gopichandran; Ranganathan, Shoba.

In: BMC Bioinformatics, Vol. 16, S8, 09.12.2015, p. 1-8.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Ranganathan, Shoba

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PY - 2015/12/9

Y1 - 2015/12/9

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