Molecular Dynamics and Thermodynamics of Protein−RNA Interactions:  Mutation of a Conserved Aromatic Residue Modifies Stacking Interactions and Structural Adaptation in the U1A−Stem Loop 2 RNA Complex

2001 ◽  
Vol 123 (11) ◽  
pp. 2548-2551 ◽  
Author(s):  
Dukagjin M. Blakaj ◽  
Kevin J. McConnell ◽  
David L. Beveridge ◽  
Anne M. Baranger
Keyword(s):  
Molecular Dynamics ◽  
Stacking Interactions ◽  
Structural Adaptation ◽  
Stem Loop ◽  
Aromatic Residue ◽  
Rna Complex ◽  
Loop 2

scholarly journals Using All-Atom Potentials to Refine RNA Structure Predictions of SARS-CoV-2 Stem Loops

2020 ◽  
Vol 21 (17) ◽  
pp. 6188
Author(s):  
Christina Bergonzo ◽  
Andrea L. Szakal
Keyword(s):  
Molecular Dynamics ◽  
Rna Structure ◽  
Untranslated Region ◽  
Conformational Equilibrium ◽  
3D Structure ◽  
Dimethyl Sulfate ◽  
Stem Loop ◽  
Dynamics Simulations ◽  
Loop 2 ◽  
Sampling Times

A considerable amount of rapid-paced research is underway to combat the SARS-CoV-2 pandemic. In this work, we assess the 3D structure of the 5′ untranslated region of its RNA, in the hopes that stable secondary structures can be targeted, interrupted, or otherwise measured. To this end, we have combined molecular dynamics simulations with previous Nuclear Magnetic Resonance measurements for stem loop 2 of SARS-CoV-1 to refine 3D structure predictions of that stem loop. We find that relatively short sampling times allow for loop rearrangement from predicted structures determined in absence of water or ions, to structures better aligned with experimental data. We then use molecular dynamics to predict the refined structure of the transcription regulatory leader sequence (TRS-L) region which includes stem loop 3, and show that arrangement of the loop around exchangeable monovalent potassium can interpret the conformational equilibrium determined by in-cell dimethyl sulfate (DMS) data.

scholarly journals Activation of viral transcription by stepwise largescale folding of an RNA virus genome

2020 ◽  
Vol 48 (16) ◽  
pp. 9285-9300
Author(s):  
Tamari Chkuaseli ◽  
K Andrew White
Keyword(s):  
Rna Structure ◽  
Rna Viruses ◽  
Rna Virus ◽  
Initial Step ◽  
Binding Pocket ◽  
Regulatory Elements ◽  
Virus Genome ◽  
Genomic Rna ◽  
Stem Loop ◽  
Rna Complex

Abstract The genomes of RNA viruses contain regulatory elements of varying complexity. Many plus-strand RNA viruses employ largescale intra-genomic RNA-RNA interactions as a means to control viral processes. Here, we describe an elaborate RNA structure formed by multiple distant regions in a tombusvirus genome that activates transcription of a viral subgenomic mRNA. The initial step in assembly of this intramolecular RNA complex involves the folding of a large viral RNA domain, which generates a discontinuous binding pocket. Next, a distally-located protracted stem-loop RNA structure docks, via base-pairing, into the binding site and acts as a linchpin that stabilizes the RNA complex and activates transcription. A multi-step RNA folding pathway is proposed in which rate-limiting steps contribute to a delay in transcription of the capsid protein-encoding viral subgenomic mRNA. This study provides an exceptional example of the complexity of genome-scale viral regulation and offers new insights into the assembly schemes utilized by large intra-genomic RNA structures.

scholarly journals Interactive Mechanism of Potential Inhibitors with Glycosyl for SARS-CoV-2 by Molecular Dynamics Simulation

Processes ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1749
Author(s):  
Yuqi Zhang ◽  
Li Chen ◽  
Xiaoyu Wang ◽  
Yanyan Zhu ◽  
Yongsheng Liu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Small Molecules ◽  
Binding Sites ◽  
Md Simulations ◽  
Experimental Methods ◽  
Dynamics Simulation ◽  
Theoretical Research ◽  
Stacking Interactions ◽  
Receptor Binding Domain ◽  
Potential Inhibitors

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a type of Ribonucleic Acid (RNA) coronavirus and it has infected and killed many people around the world. It is reported that the receptor binding domain of the spike protein (S_RBD) of the SARS-CoV-2 virus is responsible for attachment to human angiotensin converting enzyme II (ACE2). Many researchers are attempting to search potential inhibitors for fighting SARS-CoV-2 infection using theoretical or experimental methods. In terms of experimental and theoretical research, Cefuroxime, Erythromycin, Lincomycin and Ofloxacin are the potential inhibitors of SARS-CoV-2. However, the interactive mechanism of the protein SARS-CoV-2 and the inhibitors are still elusive. Here, we investigated the interactions between S_RBD and the inhibitors using molecular dynamics (MD) simulations. Interestingly, we found that there are two binding sites of S_RBD for the four small molecules. In addition, our analysis also illustrated that hydrophobic and π-π stacking interactions play crucial roles in the interactions between S_RBD and the small molecules. In our work, we also found that small molecules with glycosyl group have more effect on the conformation of S_RBD than other inhibitors, and they are also potential inhibitors for the genetic variants of SARS-CoV-2. This study provides in silico-derived mechanistic insights into the interactions of S_RBD and inhibitors, which may provide new clues for fighting SARS-CoV-2 infection.

scholarly journals Analyzing In Silico the Relationship Between the Activation of the Edema Factor and Its Interaction With Calmodulin

2020 ◽  
Vol 7 ◽  
Author(s):  
Irène Pitard ◽  
Damien Monet ◽  
Pierre L. Goossens ◽  
Arnaud Blondel ◽  
Thérèse E. Malliavin
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bonds ◽  
Md Simulations ◽  
Catalytic Site ◽  
Stacking Interactions ◽  
Long Distance ◽  
Edema Factor ◽  
Allosteric Communication ◽  
Network Of Hydrogen Bonds ◽  
The Relationship

Molecular dynamics (MD) simulations have been recorded on the complex between the edema factor (EF) of Bacilllus anthracis and calmodulin (CaM), starting from a structure with the orthosteric inhibitor adefovir bound in the EF catalytic site. The starting structure has been destabilized by alternately suppressing different co-factors, such as adefovir ligand or ions, revealing several long-distance correlations between the conformation of CaM, the geometry of the CaM/EF interface, the enzymatic site and the overall organization of the complex. An allosteric communication between CaM/EF interface and the EF catalytic site, highlighted by these correlations, was confirmed by several bioinformatics approaches from the literature. A network of hydrogen bonds and stacking interactions extending from the helix V of of CaM, and the residues of the switches A, B and C, and connecting to catalytic site residues, is a plausible candidate for the mediation of allosteric communication. The greatest variability in volume between the different MD conditions was also found for cavities present at the EF/CaM interface and in the EF catalytic site. The similarity between the predictions from literature and the volume variability might introduce the volume variability as new descriptor of allostery.

Probing the adsorption behavior and free energy landscape of single–stranded DNA oligonucleotides on single–layer MoS2 with molecular dynamics

2021 ◽  
Author(s):  
Nabanita Saikia
Keyword(s):  
Molecular Dynamics ◽  
Conformational Changes ◽  
Transition Metal Dichalcogenides ◽  
Single Layer ◽  
Adsorption Behavior ◽  
Aqueous Environment ◽  
Stacking Interactions ◽  
Single Stranded Dna ◽  
Π Stacking ◽  
Functional Dna

Abstract Interfacing single–stranded DNA (ssDNA) with 2D transition metal dichalcogenides are important for numerous technological advancements. However, the molecular mechanism of this process, including the nature of intermolecular association and conformational details of the self–assembled hybrids is still not well understood. Here, atomistic Molecular Dynamics (MD) simulation is employed to study the distinct adsorption behavior of ssDNA on a single–layer MoS2 in aqueous environment. The ssDNA sequences [T10, G10, A10, C10, U10, (GT)5, and (AC)5] are chosen on the basis that short ssDNA segments can undergo a spontaneous conformational change upon adsorption and allow efficient sampling of the conformational landscape. Differences in hybridization is attributed to the inherent molecular recognition ability of the bases. While the binding appears to be primarily driven by energetically favorable van der Waals π–stacking interactions, equilibrium structures are modulated by the ssDNA conformational changes. The poly–purines demonstrate two concurrently competing π–stacking interactions: nucleobase–nucleobase (intramolecular) and nucleobase–MoS2 (intermolecular). The poly–pyrimidines, on the other hand, reveal enhanced π–stacking interactions, thereby maximizing the number of contacts. The results provide new molecular–level understanding of ssDNA adsorption on the MoS2 surface and facilitate future studies in design of functional DNA/MoS2 structure–based platforms for DNA sequencing, biosensing (optical, electrochemical, and electronic), and drug delivery.

Exploiting hydrogen bonding interactions to probe smaller linear and cyclic diamines binding to G-quadruplexes: a DFT and molecular dynamics study

2017 ◽  
Vol 19 (18) ◽  
pp. 11474-11484 ◽  
Author(s):  
Mrinal Kanti Si ◽  
Anik Sen ◽  
Bishwajit Ganguly
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bonding ◽  
Binding Motif ◽  
Stacking Interactions ◽  
Hydrogen Bonding Interactions ◽  
Π Stacking ◽  
G Quadruplex

This report reveals that hydrogen bonding interactions between the ligand and G-quadruplex can initiate an alternative binding motif to typical π-stacking interactions.

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