Chapter 7
Network Re-Wiring During Allostery and Protein-Protein
Interactions: A Graph Spectral Approach
Vasundhara Gadiyaram, Anasuya Dighe, Sambit Ghosh,
and Saraswathi Vishveshwara
Abstract
The process of allostery is often guided by subtle changes in the non-covalent interactions between residues
of a protein. These changes may be brought about by minor perturbations by natural processes like binding
of a ligand or protein-protein interaction. The challenge lies in capturing minute changes at the residue
interaction level and following their propagation at local as well as global distances. While macromolecular
effects of the phenomenon of allostery are inferred from experiments, a computational microscope can
elucidate atomistic-level details leading to such macromolecular effects. Network formalism has served as an
attractive means to follow this path and has been pursued further for the past couple of decades. In this
chapter some concepts and methods are summarized, and recent advances are discussed. Specifically, the
changes in strength of interactions (edge weight) and their repercussion on the overall protein organization
(residue clustering) are highlighted. In this review, we adopt a graph spectral method to probe these subtle
changes in a quantitative manner. Further, the power of this method is demonstrated for capturing
re-ordering of side-chain interactions in response to ligand binding, which culminates into formation of a
protein-protein complex in β 2 -adrenergic receptors.
Key words Graph theory, Allostery, Protein structure networks, Protein-protein interactions, Sidechain interactions, Weighted networks, Spectral decomposition, Laplacian matrix
1 Introduction
Biology is anchored on the flow of information between macromolecules. These cascades of information exchange are orchestrated at multiple levels and collectively build up to a biological
entity. At the heart of this lie protein-protein interactions (PPIs).
The overarching factors which characterize PPIs and their interaction interface can be broadly classified into size and shape, surface
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_7, © Springer Science+Business Media, LLC, part of Springer Nature 2021
Vasundhara Gadiyaram and Anasuya Dighe contributed equally to the work.
Electronic supplementary material: The online version of this chapter (https://doi.org/10.1007/978-1-07161154-8_7) contains supplementary material, which is available to authorized users.
89
Network Re-Wiring During Allostery and Protein-Protein
Interactions: A Graph Spectral Approach
Vasundhara Gadiyaram, Anasuya Dighe, Sambit Ghosh,
and Saraswathi Vishveshwara
Abstract
The process of allostery is often guided by subtle changes in the non-covalent interactions between residues
of a protein. These changes may be brought about by minor perturbations by natural processes like binding
of a ligand or protein-protein interaction. The challenge lies in capturing minute changes at the residue
interaction level and following their propagation at local as well as global distances. While macromolecular
effects of the phenomenon of allostery are inferred from experiments, a computational microscope can
elucidate atomistic-level details leading to such macromolecular effects. Network formalism has served as an
attractive means to follow this path and has been pursued further for the past couple of decades. In this
chapter some concepts and methods are summarized, and recent advances are discussed. Specifically, the
changes in strength of interactions (edge weight) and their repercussion on the overall protein organization
(residue clustering) are highlighted. In this review, we adopt a graph spectral method to probe these subtle
changes in a quantitative manner. Further, the power of this method is demonstrated for capturing
re-ordering of side-chain interactions in response to ligand binding, which culminates into formation of a
protein-protein complex in β 2 -adrenergic receptors.
Key words Graph theory, Allostery, Protein structure networks, Protein-protein interactions, Sidechain interactions, Weighted networks, Spectral decomposition, Laplacian matrix
1 Introduction
Biology is anchored on the flow of information between macromolecules. These cascades of information exchange are orchestrated at multiple levels and collectively build up to a biological
entity. At the heart of this lie protein-protein interactions (PPIs).
The overarching factors which characterize PPIs and their interaction interface can be broadly classified into size and shape, surface
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_7, © Springer Science+Business Media, LLC, part of Springer Nature 2021
Vasundhara Gadiyaram and Anasuya Dighe contributed equally to the work.
Electronic supplementary material: The online version of this chapter (https://doi.org/10.1007/978-1-07161154-8_7) contains supplementary material, which is available to authorized users.
89