Interfaces Between Alpha-helical Integral Membrane Proteins: Characterization, Prediction, and Docking
Protein-protein interaction (PPI) is an essential mechanism by which proteins perform their biological functions. For globular proteins, the molecular characteristics of such interactions have been well analyzed, and many computational tools are available for predicting PPI sites and constructing st...
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doaj-ab2edc1e167f41d2854ce4d55b211e792020-11-25T00:45:35ZengElsevierComputational and Structural Biotechnology Journal2001-03702019-01-0117699711Interfaces Between Alpha-helical Integral Membrane Proteins: Characterization, Prediction, and DockingBian Li0Jeffrey Mendenhall1Jens Meiler2Department of Chemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USADepartment of Chemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USACorresponding author at: 465 21st Ave South, BIOSCI/MRBIII, Room 5144B, Nashville, TN 37232-8725, USA.; Department of Chemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USAProtein-protein interaction (PPI) is an essential mechanism by which proteins perform their biological functions. For globular proteins, the molecular characteristics of such interactions have been well analyzed, and many computational tools are available for predicting PPI sites and constructing structural models of the complex. In contrast, little is known about the molecular features of the interaction between integral membrane proteins (IMPs) and few methods exist for constructing structural models of their complexes. Here, we analyze the interfaces from a non-redundant set of complexes of α-helical IMPs whose structures have been determined to a high resolution. We find that the interface is not significantly different from the rest of the surface in terms of average hydrophobicity. However, the interface is significantly better conserved and, on average, inter-subunit contacting residue pairs correlate more strongly than non-contacting pairs, especially in obligate complexes. We also develop a neural network-based method, with an area under the receiver operating characteristic curve of 0.75 and a Pearson correlation coefficient of 0.70, for predicting interface residues and their weighted contact numbers (WCNs). We further show that predicted interface residues and their WCNs can be used as restraints to reconstruct the structure α-helical IMP dimers through docking for fourteen out of a benchmark set of sixteen complexes. The RMSD100 values of the best-docked ligand subunit to its native structure are <2.5 Å for these fourteen cases. The structural analysis conducted in this work provides molecular details about the interface between α-helical IMPs and the WCN restraints represent an efficient means to score α-helical IMP docking candidates. Keywords: Membrane protein interfaces, Membrane protein docking, Neural networks, Weighted contact numbershttp://www.sciencedirect.com/science/article/pii/S200103701930039X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bian Li Jeffrey Mendenhall Jens Meiler |
spellingShingle |
Bian Li Jeffrey Mendenhall Jens Meiler Interfaces Between Alpha-helical Integral Membrane Proteins: Characterization, Prediction, and Docking Computational and Structural Biotechnology Journal |
author_facet |
Bian Li Jeffrey Mendenhall Jens Meiler |
author_sort |
Bian Li |
title |
Interfaces Between Alpha-helical Integral Membrane Proteins: Characterization, Prediction, and Docking |
title_short |
Interfaces Between Alpha-helical Integral Membrane Proteins: Characterization, Prediction, and Docking |
title_full |
Interfaces Between Alpha-helical Integral Membrane Proteins: Characterization, Prediction, and Docking |
title_fullStr |
Interfaces Between Alpha-helical Integral Membrane Proteins: Characterization, Prediction, and Docking |
title_full_unstemmed |
Interfaces Between Alpha-helical Integral Membrane Proteins: Characterization, Prediction, and Docking |
title_sort |
interfaces between alpha-helical integral membrane proteins: characterization, prediction, and docking |
publisher |
Elsevier |
series |
Computational and Structural Biotechnology Journal |
issn |
2001-0370 |
publishDate |
2019-01-01 |
description |
Protein-protein interaction (PPI) is an essential mechanism by which proteins perform their biological functions. For globular proteins, the molecular characteristics of such interactions have been well analyzed, and many computational tools are available for predicting PPI sites and constructing structural models of the complex. In contrast, little is known about the molecular features of the interaction between integral membrane proteins (IMPs) and few methods exist for constructing structural models of their complexes. Here, we analyze the interfaces from a non-redundant set of complexes of α-helical IMPs whose structures have been determined to a high resolution. We find that the interface is not significantly different from the rest of the surface in terms of average hydrophobicity. However, the interface is significantly better conserved and, on average, inter-subunit contacting residue pairs correlate more strongly than non-contacting pairs, especially in obligate complexes. We also develop a neural network-based method, with an area under the receiver operating characteristic curve of 0.75 and a Pearson correlation coefficient of 0.70, for predicting interface residues and their weighted contact numbers (WCNs). We further show that predicted interface residues and their WCNs can be used as restraints to reconstruct the structure α-helical IMP dimers through docking for fourteen out of a benchmark set of sixteen complexes. The RMSD100 values of the best-docked ligand subunit to its native structure are <2.5 Å for these fourteen cases. The structural analysis conducted in this work provides molecular details about the interface between α-helical IMPs and the WCN restraints represent an efficient means to score α-helical IMP docking candidates. Keywords: Membrane protein interfaces, Membrane protein docking, Neural networks, Weighted contact numbers |
url |
http://www.sciencedirect.com/science/article/pii/S200103701930039X |
work_keys_str_mv |
AT bianli interfacesbetweenalphahelicalintegralmembraneproteinscharacterizationpredictionanddocking AT jeffreymendenhall interfacesbetweenalphahelicalintegralmembraneproteinscharacterizationpredictionanddocking AT jensmeiler interfacesbetweenalphahelicalintegralmembraneproteinscharacterizationpredictionanddocking |
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1725269325878657024 |