Chapter 3
Identification of Allosteric Effects in Proteins by Elastic
Network Models
Guang Hu
Abstract
Allostery is a fundamental regulatory mechanism in the majority of biological processes of molecular
machines. Allostery is well-known as a dynamic-driven process, and thus, the molecular mechanism of
allosteric signal transmission needs to be established. Elastic network models (ENMs) provide efficient
methods for investigating the intrinsic dynamics and allosteric communication pathways in proteins. In this
chapter, two ENM methods including Gaussian network model (GNM) coupled with Markovian stochastic
model, as well as the anisotropic network model (ANM), were introduced to identify allosteric effects in
hemoglobins. Techniques on model parameters, scripting and calculation, analysis, and visualization are
shown step by step.
Key words Normal mode analysis, Global motion, Commute time, Allosteric site, Communication
pathway
1 Introduction
One of the central goals in current biology is to understand the
allosteric effects in molecular machines [1, 2]. Allostery is a fundamental process that regulates the function of proteins via a local
perturbation of one site, such as ligand binding, mutations, or
covalent modifications, which can induce a communication across
the structure to another spatially distant site [3]. Identification of
allosteric effects in proteins may help in efficient drug discovery and
protein design [4]. After the first incorporation of the concept of
allostery in describing the cooperative transition of hemoglobin
[5], different models have been proposed to understand the molecular mechanism of allosteric regulations [6]. However, two fundamental aspects in allosteric effects are still needed to be uncovered.
On the first hand, the identification of potential allosteric sites and
how to quantify their allosteric ability remains an enigma. On the
other hand, the mechanism that underlies distal communications
Luisa Di Paola and Alessandro Giuliani (eds.), Allostery: Methods and Protocols, Methods in Molecular Biology, vol. 2253,
https://doi.org/10.1007/978-1-0716-1154-8_3, © Springer Science+Business Media, LLC, part of Springer Nature 2021
21
Identification of Allosteric Effects in Proteins by Elastic
Network Models
Guang Hu
Abstract
Allostery is a fundamental regulatory mechanism in the majority of biological processes of molecular
machines. Allostery is well-known as a dynamic-driven process, and thus, the molecular mechanism of
allosteric signal transmission needs to be established. Elastic network models (ENMs) provide efficient
methods for investigating the intrinsic dynamics and allosteric communication pathways in proteins. In this
chapter, two ENM methods including Gaussian network model (GNM) coupled with Markovian stochastic
model, as well as the anisotropic network model (ANM), were introduced to identify allosteric effects in
hemoglobins. Techniques on model parameters, scripting and calculation, analysis, and visualization are
shown step by step.
Key words Normal mode analysis, Global motion, Commute time, Allosteric site, Communication
pathway
1 Introduction
One of the central goals in current biology is to understand the
allosteric effects in molecular machines [1, 2]. Allostery is a fundamental process that regulates the function of proteins via a local
perturbation of one site, such as ligand binding, mutations, or
covalent modifications, which can induce a communication across
the structure to another spatially distant site [3]. Identification of
allosteric effects in proteins may help in efficient drug discovery and
protein design [4]. After the first incorporation of the concept of
allostery in describing the cooperative transition of hemoglobin
[5], different models have been proposed to understand the molecular mechanism of allosteric regulations [6]. However, two fundamental aspects in allosteric effects are still needed to be uncovered.
On the first hand, the identification of potential allosteric sites and
how to quantify their allosteric ability remains an enigma. On the
other hand, the mechanism that underlies distal communications
Luisa Di Paola and Alessandro Giuliani (eds.), Allostery: Methods and Protocols, Methods in Molecular Biology, vol. 2253,
https://doi.org/10.1007/978-1-0716-1154-8_3, © Springer Science+Business Media, LLC, part of Springer Nature 2021
21