Towards gaining sight of multiscale events: utilizing network models and normal modes in hybrid methods

Surveying the Side-Chain Network Approach to Protein Structure and Dynamics: The SARS-CoV-2 Spike Protein as an Illustrative Case

“…et al, 2018; Astl et al, 2019;Krieger et al, 2020;Verkhivker et al, 2020). While protein backbone networks (PBN) capture the non-covalent connectivity at the level of the backbone atoms, protein side-chain networks (PScN/PSN) capture the structural connectivity at the level of non-covalent interactions between side-chain atoms.…”

“…Network theory-based analyses of protein structure (Bagler and Sinha, 2005;Atilgan et al, 2012) and dynamics have provided unprecedented insights into the global structural connectivity of proteins and its complexes in the context of allostery and other biological processes (Atilgan et al, 2012;Di Paola et al, 2013;Bhattacharyya et al, 2016;Gadiyaram et al, 2019;Krieger et al, 2020;Verkhivker et al, 2020). When combined with information on conformational variations, as obtained from molecular dynamics, network approaches have elucidated several examples of protein structure-function relationships (Doruker et al, 2000;Sethi et al, 2009;Bhattacharyya et al, 2013;Papaleo, 2015;Tse and Verkhivker, 2015;Doshi et al, 2016).…”

“…There are a number of ways to define the connectivity criteria and assign strengths of interactions. Similarly, the dynamical conformational landscape can be obtained at the explicit atomic level or indirectly achieved through methods like ENM, which provides cooperative modes of motion (Krieger et al, 2020;Zhang et al, 2020). The atomic level description can be obtained experimentally through biophysical techniques such as X-ray crystallography, cryo-EM, and NMR, and computationally through molecular dynamics (MD) simulations.…”

“…Understanding protein connectivity and dynamics can provide molecular mechanistic insights into the various biological processes, like allostery (Atilgan et al, 2007;Verkhivker et al, 2020;Wang et al, 2020a), protein-protein or protein-nucleic acid interactions Keskin et al, 2005;Sathyapriya et al, 2008;Sethi et al, 2009), and ligand/perturbation-induced conformational variations (Csermely et al, 2013;Bandaru et al, 2017;Creixell et al, 2018). Such calculations may also aid the identification of epitopes for drug-binding and capture drug-induced conformational changes in proteins and protein complexes (Csermely et al, 2013;Krieger et al, 2020).…”

Editorial: Understanding Protein Dynamics, Binding and Allostery for Drug Design

“…Normal mode analysis based on ENM facilitates the study of protein dynamics and allosteric effects in a high-throughput manner (Krieger et al, 2020). Ayyildiz et al, integrated ENM-based methods with computational solvent mapping and sequence/structural alignments for identifying potential allosteric sites.…”