Insights into the dynamics of cyclic diguanosine monophosphate I riboswitch using molecular dynamics simulation
Online Publishing @ NISCAIR
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Authentication Code |
dc |
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Title Statement |
Insights into the dynamics of cyclic diguanosine monophosphate I riboswitch using molecular dynamics simulation |
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Added Entry - Uncontrolled Name |
Kumari, Priyanka Pratap Singh, Surya Som, Anup |
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Uncontrolled Index Term |
Binding pocket; Dynamic cross correlation; Principal component analysis; Secondary and tertiary structures; Trajectory analysis |
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Summary, etc. |
Riboswitches are key cis-regulatory elements, present at 5' UTRs of several prokaryotic mRNAs, involved in gene expression regulation by binding selectively to specific ligands followed by conformational changes. However, understanding of ligand-free riboswitch, conformational changes between the ligand-free and ligand-bound riboswitch and binding mechanism of ligand to the aptamer of riboswitch is limited. In the present paper we describe the structural and dynamical properties of ligand-free c-di-GMP I riboswitch aptamer and its possible binding mechanism with c-di-GMP by means of all-atom molecular dynamics (MD) simulations. Various analyses such as principal component analysis, cross correlation dynamics analysis, network analysis and trajectory analyses were carried out. The ligand-free structure shows stable conformation with folded P2, P3 and an unwind P1 helix with open binding pocket at helix-join-helix junction while the ligand-bound structure showed closed binding pocket structure compared to the ligand-free structure. The junction residues significantly showed anti-correlations with P1 helix and weak correlated motions with each other in the open conformation of the ligand-free aptamer of riboswitch. The networks analysis of binding pocket residues suggested interaction among the identified key residues of the binding pocket (G20, A47, C92) and P1 helix illustrating the role of P1 helix in binding of ligand. The structural insights, on c-di-GMP I riboswitch, presented in this paper can be useful for the development of therapeutics against V. cholerae. The understanding of the c-di-GMP I riboswitch at dynamic molecular level provides a potential solution for riboswitch drug design. |
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Publication, Distribution, Etc. |
Indian Journal of Biochemistry and Biophysics (IJBB) 2021-06-01 14:23:30 |
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Electronic Location and Access |
application/pdf application/pdf http://op.niscair.res.in/index.php/IJBB/article/view/37679 |
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Data Source Entry |
Indian Journal of Biochemistry and Biophysics (IJBB); IJBB Vol. 58 (3) [June 2021] |
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Language Note |
en |
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