Chapter 10
The PyInteraph Workflow for the Study of Interaction
Networks From Protein Structural Ensembles
Matteo Lambrughi, Valentina Sora, and Matteo Tiberti
Abstract
PyInteraph is a software package designed for the analysis of structural communication from conformational ensembles, such as those derived from in silico simulations, under the formalism of protein structure
networks. We demonstrate its usage for the calculation and analysis of intramolecular interaction networks
derived from three different types of interactions, as well as with a more general protocol based on distances
between centers of mass. We use the xPyder PyMOL plug-in to visualize such networks on the threedimensional structure of the protein. We showcase our protocol on a molecular dynamics trajectory of the
Cyclophilin A wild-type enzyme, a well-studied protein in which different allosteric mechanisms have been
investigated.
Key words Protein structure networks, PSN, Structural communication, Allostery, Salt bridge,
Hydrogen bond, Atomic contact, Non-covalent interaction, Graph
1 Introduction
1.1 Long-Range
Structural
Communication in
Proteins
Localized changes in the structure of a protein can influence distant
regions, resulting in sometimes dramatic changes far from the site
of the perturbation in terms of both structure and dynamics. Such
perturbations can be, for instance, the binding of a small molecule
as inhibitor or effector, but also a mutation or a post-translational
modification [1–3]. The localized perturbation at a site imposes
stress on the protein structure and changes in dynamics, and such
changes propagate throughout the structure to other parts of the
protein. The transmission of structural information happens
through pathways of interconnected residues that are
pre-encoded in the structural ensemble and can be one or more
likely several. Mutations in these communication routes may affect
the propagation of the signal [4]. In this sense, dynamical motions
and intra-residue contacts are the underlying substrates through
which structural communication happens.
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_10, © Springer Science+Business Media, LLC, part of Springer Nature 2021
153
The PyInteraph Workflow for the Study of Interaction
Networks From Protein Structural Ensembles
Matteo Lambrughi, Valentina Sora, and Matteo Tiberti
Abstract
PyInteraph is a software package designed for the analysis of structural communication from conformational ensembles, such as those derived from in silico simulations, under the formalism of protein structure
networks. We demonstrate its usage for the calculation and analysis of intramolecular interaction networks
derived from three different types of interactions, as well as with a more general protocol based on distances
between centers of mass. We use the xPyder PyMOL plug-in to visualize such networks on the threedimensional structure of the protein. We showcase our protocol on a molecular dynamics trajectory of the
Cyclophilin A wild-type enzyme, a well-studied protein in which different allosteric mechanisms have been
investigated.
Key words Protein structure networks, PSN, Structural communication, Allostery, Salt bridge,
Hydrogen bond, Atomic contact, Non-covalent interaction, Graph
1 Introduction
1.1 Long-Range
Structural
Communication in
Proteins
Localized changes in the structure of a protein can influence distant
regions, resulting in sometimes dramatic changes far from the site
of the perturbation in terms of both structure and dynamics. Such
perturbations can be, for instance, the binding of a small molecule
as inhibitor or effector, but also a mutation or a post-translational
modification [1–3]. The localized perturbation at a site imposes
stress on the protein structure and changes in dynamics, and such
changes propagate throughout the structure to other parts of the
protein. The transmission of structural information happens
through pathways of interconnected residues that are
pre-encoded in the structural ensemble and can be one or more
likely several. Mutations in these communication routes may affect
the propagation of the signal [4]. In this sense, dynamical motions
and intra-residue contacts are the underlying substrates through
which structural communication happens.
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_10, © Springer Science+Business Media, LLC, part of Springer Nature 2021
153