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Methods for Detecting Protein Binding Interfaces

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Computer-Aided Drug Discovery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

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Abstract

Protein molecules often come together in complexes in order to achieve their biological functions in the living cell. Since the three-dimensional structure and the functionality of proteins are closely related to each other, characterizing the structural and dynamical properties of protein complexes through experiments or computational modeling is important for understanding their roles in the basic biology of organisms. Certain specific regions of a protein may play a critical role in its structural, dynamical, and functional properties. A protein molecule binds to another protein or to a drug molecule through a specific site on its surface, which is commonly known as the binding interface. Prediction of binding interfaces can assist in drug design, protein engineering, protein function elucidation, molecular docking, and analyzing the networks of protein-protein interactions. Experimental detection of binding interfaces can provide a wealth of information, but is time consuming and sometimes inaccurate. Computational methods can validate and complement experimental studies in a cost-efficient way. In this chapter we present a short survey of computational methods that have been suggested over the past two decades for the detection of protein-protein and protein-drug binding interfaces, focusing on methods that use specific amino acids as determinants of binding interfaces. Later, we describe our work in using evolutionary conservation and structural features to detect binding interfaces in proteins and guide protein-protein docking.

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Acknowledgements

The work described here was partially funded by NSF grant CCF-1116060. The author thanks Dr. Bahar Akbal-Delibas, Dr. Filip Jagodzinski, Dr. Amarda Shehu, and Irina Hashmi for their collaboration. The computations were carried out in part using the UMB research cluster.

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Authors and Affiliations

  1. Department of Computer Science, University of Massachusetts Boston, Boston, MA, 02125, USA

    Nurit Haspel

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  1. Nurit Haspel
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Correspondence to Nurit Haspel .

Editor information

Editors and Affiliations

  1. Chemistry Department, Southern Research Institute, Birmingham, Alabama, USA

    Wei Zhang

Glossary

AI

Artificial intelligence

lRMSD

Least root mean square deviation

PDB

Protein Data Bank

SVM

Support vector machine

VdW

van der Waals

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Haspel, N. (2015). Methods for Detecting Protein Binding Interfaces. In: Zhang, W. (eds) Computer-Aided Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/7653_2015_48

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  • DOI: https://doi.org/10.1007/7653_2015_48

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3519-2

  • Online ISBN: 978-1-4939-3521-5

  • eBook Packages: Springer Protocols

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