Chapter 9
Community Network Analysis of Allosteric Proteins
Ivan Rivalta and Victor S. Batista
Abstract
Community network analysis (CNA) of correlated protein motions allows modeling of signals propagation
in allosteric proteic systems. From standard classical molecular dynamics (MD) simulations, protein
motions can be analysed by means of mutual information between pairs of amino acid residues, providing
dynamical weighted networks that contains fundamental information of the communication among amino
acids. The CNA method has been successfully applied to a variety of allosteric systems including an enzyme,
a nuclear receptor and a bacterial adaptive immune system, providing characterization of the allosteric
pathways. This method is complementary to network analyses based on different metrics and it is particularly powerful for studying large proteic systems, as it provides a coarse-grained view of the communication
flows within large and complex networks.
Key words Protein correlated motions, Allosteric enzyme, Protein graph, Community network
analysis, Allosteric pathways
1 Introduction
Understanding protein allostery is hindered by the complex and
elusive nature of the allosteric mechanisms in proteic systems
[1]. In fact, despite pioneering allostery models date more than
half a century back [2] and the distinct views developed so far have
been recently unified [3, 4], many aspects of allosteric phenomena
remain poorly understood [5]. In particular, considering the ubiquitous role of allostery in biological systems, it is highly desirable to
fully exploit its potential for rational drug design and protein
engineering [6–8]. For instance, allosteric enzymes could be
manipulated to inhibit/enhance their enzymatic activity by point
mutagenesis or by binding of exogenous allosteric ligands (effectors) and/or by disclosing unknown allosteric sites [9–12]. To his
aim, computer simulations represent an exceptional tool that can
provide the necessary system-specific information for rational
design, avoiding extended (and costly) trial-and-error
investigations.
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_9, © Springer Science+Business Media, LLC, part of Springer Nature 2021
137
Community Network Analysis of Allosteric Proteins
Ivan Rivalta and Victor S. Batista
Abstract
Community network analysis (CNA) of correlated protein motions allows modeling of signals propagation
in allosteric proteic systems. From standard classical molecular dynamics (MD) simulations, protein
motions can be analysed by means of mutual information between pairs of amino acid residues, providing
dynamical weighted networks that contains fundamental information of the communication among amino
acids. The CNA method has been successfully applied to a variety of allosteric systems including an enzyme,
a nuclear receptor and a bacterial adaptive immune system, providing characterization of the allosteric
pathways. This method is complementary to network analyses based on different metrics and it is particularly powerful for studying large proteic systems, as it provides a coarse-grained view of the communication
flows within large and complex networks.
Key words Protein correlated motions, Allosteric enzyme, Protein graph, Community network
analysis, Allosteric pathways
1 Introduction
Understanding protein allostery is hindered by the complex and
elusive nature of the allosteric mechanisms in proteic systems
[1]. In fact, despite pioneering allostery models date more than
half a century back [2] and the distinct views developed so far have
been recently unified [3, 4], many aspects of allosteric phenomena
remain poorly understood [5]. In particular, considering the ubiquitous role of allostery in biological systems, it is highly desirable to
fully exploit its potential for rational drug design and protein
engineering [6–8]. For instance, allosteric enzymes could be
manipulated to inhibit/enhance their enzymatic activity by point
mutagenesis or by binding of exogenous allosteric ligands (effectors) and/or by disclosing unknown allosteric sites [9–12]. To his
aim, computer simulations represent an exceptional tool that can
provide the necessary system-specific information for rational
design, avoiding extended (and costly) trial-and-error
investigations.
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_9, © Springer Science+Business Media, LLC, part of Springer Nature 2021
137