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An assessment of protein–ligand binding site polarizability

An assessment of protein–ligand binding site polarizability Electronic polarizability, an important physical property of biomolecules, is currently ignored in most biomolecular calculations. Yet, it is widely believed that polarization could account for a substantial fraction of the total nonbonded energy of a system. This belief is supported by studies of small complexes in vacuum. This perception is driving the development of a new class of polarizable force fields for biomolecular calculations. However, the quantification of this term for protein–ligand complexes has never been attempted. Here we explore the polarizable nature of protein–ligand complexes in order to evaluate the importance of this effect. We introduce two indexes describing the polarizability of protein binding sites. These we apply to a large range of pharmaceutically relevant complexes. We offer a recommendation of particular complexes as test systems with which to determine the effects of polarizability and as test cases with which to test the new generation of force fields. Additionally, we provide a tabulation of the amino acid composition of these binding sites and show that composition can be specific for certain classes of proteins. We also show that the relative abundance of some amino acids is different in binding sites than elsewhere in a protein's structure. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 201–211, 2003 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biopolymers Wiley

An assessment of protein–ligand binding site polarizability

Nayeem, Akbar; Krystek, Stanley; Stouch, Terry
Biopolymers , Volume 70 (2) – Oct 1, 2003
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References (64)

Publisher
Wiley
Copyright
Copyright © 2003 Wiley Periodicals, Inc., A Wiley Company
ISSN
0006-3525
eISSN
1097-0282
DOI
10.1002/bip.10434
pmid
14517908
Publisher site
See Article on Publisher Site

Abstract

Electronic polarizability, an important physical property of biomolecules, is currently ignored in most biomolecular calculations. Yet, it is widely believed that polarization could account for a substantial fraction of the total nonbonded energy of a system. This belief is supported by studies of small complexes in vacuum. This perception is driving the development of a new class of polarizable force fields for biomolecular calculations. However, the quantification of this term for protein–ligand complexes has never been attempted. Here we explore the polarizable nature of protein–ligand complexes in order to evaluate the importance of this effect. We introduce two indexes describing the polarizability of protein binding sites. These we apply to a large range of pharmaceutically relevant complexes. We offer a recommendation of particular complexes as test systems with which to determine the effects of polarizability and as test cases with which to test the new generation of force fields. Additionally, we provide a tabulation of the amino acid composition of these binding sites and show that composition can be specific for certain classes of proteins. We also show that the relative abundance of some amino acids is different in binding sites than elsewhere in a protein's structure. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 201–211, 2003

Journal

Biopolymers – Wiley

Published: Oct 1, 2003

Keywords: polarizability; force fields; molecular modeling; molecular mechanics; ligand binding; binding energy

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