Allostery is described as action at a distance. The end result of a stimulus may be mediated through a dramatic conformational change or subtle global changes in the protein. A perspective based on side-chain networks can provide valuable insights into the differences in global connectivity features between various dynamical states of a protein. This is especially important to capture subtle conformational changes. In light of the COVID-19 pandemic, we focus on characterizing the global features of SARS-Cov2 (COVID-19) spike glycoprotein. Our objective is to review and apply our network approaches to gain insights into a key viral protein at the structural level. We employ dynamical side-chain network concepts on COVID-19 spike glycoprotein, which is crucial for viral entry into human cells. As expected, there are considerable similarities of network metrics between the partially open and the closed states of the trimeric SARS-CoV2 spike protein . However, there are also significant differences seen at the domain-domain interfaces within a chain and across the trimeric interface. We discuss these differences in terms of the structural-functional aspects of the spike protein. Our comprehensive presentation and application of the side chain network approach demonstrates its worth in the case of the spike protein. The analyses of the network parameters show that the residues at the receptor binding domain and at the cell fusion level do not act locally but are supported by extensive global side-chain networks. Sequence comparison with SARS-Cov1 shows that the residue level network metrics such as hubs, cliques/communities are mostly conserved in the two proteins. Our analysis reflects the paramount importance of network features, implying that computational drug design strategies stand to greatly benefit by exploiting them .
Network theory-based approaches provide valuable insights into the variations in global structural connectivity between differing dynamical states of proteins. Our objective is to review network-based analyses to elucidate such variations, especially in the context of subtle conformational changes. We present technical details of the construction and analyses of protein structure networks, encompassing both the non-covalent connectivity and dynamics. We examine the selection of optimal criteria for connectivity based on the physical concept of percolation. We highlight the advantages of using side-chain based network metrics in contrast to backbone measurements. As an illustrative example, we apply the described network approach to investigate the global conformational change between the closed and partially open states of the SARS-CoV-2 spike protein. This conformational change in the spike protein is crucial for coronavirus entry and fusion into human cells. Our analysis reveals global structural reorientations between the two states of the spike protein despite small changes between the two states at the backbone level. We also observe some differences at strategic locations in the structures, correlating with their functions, asserting the advantages of the side-chain network analysis. Finally we present a view of allostery as a subtle synergistic-global change between the ligand and the receptor, the incorporation of which would enhance the drug design strategies .
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Allostery is described as action at a distance. The end result of a stimulus may be mediated through a dramatic conformational change or subtle global changes in the protein. A perspective based on side-chain networks can
Network theory-based approaches
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differences in global connectivity features between various
variations in global structural connectivity between differing
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a protein. This is especially important to capture
proteins. Our objective is to review network-based analyses to elucidate such variations, especially in the context of
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In light of the COVID-19 pandemic, we focus on characterizing the global features of SARS-Cov2 (COVID-19) spike glycoprotein. Our objective is to review and apply our network approaches to gain insights into a key viral protein at the structural level. We employ dynamical
We present technical details of the construction and analyses of protein structure networks, encompassing both the non-covalent connectivity and dynamics. We examine the selection of optimal criteria for connectivity based on the physical concept of percolation. We highlight the advantages of using
R
network concepts on COVID-19 spike glycoprotein, which
based network metrics in contrast to backbone measurements. As an illustrative example, we apply the described network approach to investigate the global conformational change between the closed and partially open states of the SARS-CoV-2 spike protein. This conformational change in the spike protein
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viral entry
coronavirus entry and fusion
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As expected, there are considerable similarities of network metrics between the partially open and the closed
Our analysis reveals global structural reorientations between the two
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trimeric SARS-CoV2 spike protein . However, there are also significant differences seen at the domain-domain interfaces within a chain and across the trimeric interface. We discuss these differences in terms of the structural-functional aspects of the spike protein. Our comprehensive presentation and application of the side chain network approach demonstrates its worth in the case of the spike protein. The analyses of
spike protein despite small changes between the two states at the backbone level. We also observe some differences at strategic locations in
R
network parameters show that the residues at the receptor binding domain and at the cell fusion level do not act locally but are supported by extensive global side-chain networks. Sequence comparison with SARS-Cov1 shows that the residue level network metrics such as hubs, cliques/communities are mostly conserved in the two proteins. Our analysis reflects the paramount importance of network features, implying that computational
structures, correlating with their functions, asserting the advantages of the side-chain network analysis. Finally we present a view of allostery as a subtle synergistic-global change between the ligand and the receptor, the incorporation of which would enhance the
D
stand to greatly benefit by exploiting them