ABSTRACT
The structural variation of RNA is often very transient and can be easily missed in experiments. Molecular dynamics simulation studies along with network analysis can be an effective tool to identify prominent conformations of such dynamic biomolecular systems. Here we describe a method to effectively sample different RNA conformations at six different temperatures based on the changes in the interhelical orientations. This method gives the information about prominent states of the RNA as well as the probability of the existence of different conformations and their interconnections during the process of evolution. In the case of the SARS-CoV-2 genome, the change of prominent structures was found to be faster at 333 K as compared to higher temperatures due to the formation of the non-native base pairs. ΔΔG calculated between 288 K and 363 K are found to be 10.31 kcal/mol (88 nt) considering the contribution from the multiple states of the RNA which agrees well with the experimentally reported denaturation energy for E. coli α mRNA pseudoknot (â¼16 kcal/mol, 112 nt) determined by calorimetry/UV hyperchromicity and human telomerase RNA telomerase (4.5-6.6 kcal/mol, 54 nt) determined by FRET analysis.
Subject(s)
COVID-19 , Escherichia coli , Humans , Molecular Dynamics Simulation , Nucleic Acid Conformation , RNA/chemistry , RNA/genetics , SARS-CoV-2/genetics , ThermodynamicsABSTRACT
Understanding the dynamics of the SARS CoV-2 RNA genome and its dependence on temperature is necessary to fight the current COVID-19 crisis. Computationally, the handling of large data is a major challenge in the elucidation of the structures of RNA. This work presents network analysis as an important tool to see the conformational evolution and the most dominant structures of the RNA genome at six different temperatures. It effectively distinguished different communities of RNA having structural variation. It is found that at higher temperatures (348 K and above), 80% of the RNA structure is destroyed in both the SPC/E and mTIP3P water models. The thermal denaturation free energy change ΔΔG value calculated for the long-lived structure at higher temperatures of 348 and 363 K ranges from 2.58 to 2.78 kcal/mol for the SPC/E water model, which agrees well with the experimentally reported thermal denaturation free energy range of 2.874 kcal/mol of SARS CoV-NP at normal pH. At higher temperatures, the stability of RNA conformation is found to be due to the existence of non-native base pairs in the SPC/E water model.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Nucleic Acid Conformation , RNA , TemperatureABSTRACT
The COVID-19 epidemic has presented many treatment challenges to physicians due to the lack of specific effective medicines. The COVID-19 pandemic is also witnessing irrational antibiotic use. The aggressive use of several antibiotics for treatment of COVID-19, and its complications may lead to another pandemic of Antimicrobial Resistance (AMR). Limiting unnecessary antibiotic use in viral infections, like COVID-19, should be emphasized in antimicrobial stewardship programs.