Chapter 2
Disclosing Allostery Through Protein Contact Networks
Luisa Di Paola, Giampiero Mei, Almerinda Di Venere,
and Alessandro Giuliani
Abstract
Proteins are located in the twilight zone between chemistry and biology, where a peculiar kind of
complexity starts. Proteins are the smallest ‘devices’ showing a sensible adaptation to their environment
by the production of appropriate behavior when facing a specific stimulus. This fact qualifies (from the
‘effector’ side) proteins as nanomachines working as catalysts, motors, or switches. However (from the
sensor side), the need to single out the ‘specific stimulus’ out of thermal noise qualifies proteins as
information processing devices. Allostery corresponds to the modification of the configuration (in a
broad sense) of the protein molecule in response to a specific stimulus in a non-strictly local way, thereby
connecting the sensor and effector sides of the nanomachine. This is why the ‘disclosing’ of allostery
phenomenon is at the very heart of protein function; in this chapter, we will demonstrate how a networkbased representation of protein structure in terms of nodes (aminoacid residues) and edges (effective
contacts between residues) is the natural language for getting rid of allosteric phenomena and, more in
general, of protein structure/function relationships.
Key words Protein contact networks, Network descriptors, Spectral clustering
1 Introduction
Allostery is a neologism modeled upon Greek language, which has
to do with the ability of proteins to transmit a signal from one site
to another in response to environmental stimuli. This ability is
related to the transmission of information across the protein molecule from a sensor (allosteric) site to the effector (binding) site
[1]. The molecule, hence, perceives ligand binding at a distance
from the active site, or any other microenvironmental perturbation,
like pH changes. The information transfer across protein molecules
can be approached by many different methods going from experimental (change in affinity of the enzymatic systems upon allosteric
stimulus exposition) to structural (comparison of X-ray or NMR
structures correspondent to different activation states) and theoretical (molecular dynamics simulation of allosteric agent binding)
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_2, © Springer Science+Business Media, LLC, part of Springer Nature 2021
7
Disclosing Allostery Through Protein Contact Networks
Luisa Di Paola, Giampiero Mei, Almerinda Di Venere,
and Alessandro Giuliani
Abstract
Proteins are located in the twilight zone between chemistry and biology, where a peculiar kind of
complexity starts. Proteins are the smallest ‘devices’ showing a sensible adaptation to their environment
by the production of appropriate behavior when facing a specific stimulus. This fact qualifies (from the
‘effector’ side) proteins as nanomachines working as catalysts, motors, or switches. However (from the
sensor side), the need to single out the ‘specific stimulus’ out of thermal noise qualifies proteins as
information processing devices. Allostery corresponds to the modification of the configuration (in a
broad sense) of the protein molecule in response to a specific stimulus in a non-strictly local way, thereby
connecting the sensor and effector sides of the nanomachine. This is why the ‘disclosing’ of allostery
phenomenon is at the very heart of protein function; in this chapter, we will demonstrate how a networkbased representation of protein structure in terms of nodes (aminoacid residues) and edges (effective
contacts between residues) is the natural language for getting rid of allosteric phenomena and, more in
general, of protein structure/function relationships.
Key words Protein contact networks, Network descriptors, Spectral clustering
1 Introduction
Allostery is a neologism modeled upon Greek language, which has
to do with the ability of proteins to transmit a signal from one site
to another in response to environmental stimuli. This ability is
related to the transmission of information across the protein molecule from a sensor (allosteric) site to the effector (binding) site
[1]. The molecule, hence, perceives ligand binding at a distance
from the active site, or any other microenvironmental perturbation,
like pH changes. The information transfer across protein molecules
can be approached by many different methods going from experimental (change in affinity of the enzymatic systems upon allosteric
stimulus exposition) to structural (comparison of X-ray or NMR
structures correspondent to different activation states) and theoretical (molecular dynamics simulation of allosteric agent binding)
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_2, © Springer Science+Business Media, LLC, part of Springer Nature 2021
7