Effect of Ions and Temperature on the Structural and Dynamic Aspects of Biomolecules

Abstract

The atomic-level structural and dynamical study of biomacromolecules to understand the biomolecular mechanisms poses a major challenge in molecular biophysics. The biological activity of many macromolecules in the cellular environment depends on the individual or combined effect of external factors such as the presence of mono/di-valent cations, water, and temperature. These factors can trigger the constant motion of the atoms in biomolecules due to inter and intra-molecular interactions, which in turn changes the dynamic aspects. The interactions of biomolecules and biomolecular complexes such as protein-protein, protein-DNA, and protein-RNA with water and solvent molecules have a vital role in the biological system. Water plays an important role in biological processes as a primary solvent. The structure of liquid water can be altered due to its interaction with biomolecules, metal ions, cosolvents, and under thermodynamic conditions. In principle, Molecular Dynamics simulations typically generate substantial insight into biomolecular functions by providing the dynamics of water/hydrated ions and their interactions with the biomolecules. Also, the formation of a strong interaction between the protein-protein, protein-RNA, protein-ions, and protein-water complex can be easily predicted using computer simulations. To understand the various interactions, several protein-protein, protein-water, protein-ions, and RNA-water systems were analyzed in this research work. This includes the study of hydration shell properties near antimicrobial peptide in the presence of metal ions, the influence of the ion specificity and temperature dependence on the structure of intrinsically disordered sheep prion peptide, conformational evolution, and the effect of the ion-counter ion based on the different model potential on the stability of Frameshift Stimulation Element (FSE) of SARS CoV-2 RNA genome. The results show that the water molecules in a hydrophilic environment are more disruptive, containing broken hydrogen bonds compared to the hydrophobic environment. The hydrophilic and hydrophobic amino acids attribute to the formation of different density regions of water molecules near the peptide surface in the presence of ions. The changes in the secondary structure elements of intrinsically disordered peptides (IDP) are found to be more sensitive in the presence of ions. The transition from the disordered-to-ordered structure with temperature was thoroughly studied based on the interaction of the hydrophobic and hydrophilic residues with water. Insights into the structural changes of IDP with ions and temperature possess great clinical significance because of its pathogenicity. The temperature dependence of the FSE of the SARS CoV-2 RNA genome shows interchangeable conformations with more stability at lower temperatures compared to higher temperatures. The RNA structure was found to be more dynamic and transient in the mTIP3P water model. The formation of the ion-contact pair near the negatively charged phosphate group (Na+-PO4-) leads to strong RNA-ion interaction due to the lower dielectric constant of the SPC/E model helps to make strong hydration shells with higher hydrogen bond lifetime. The survival probability of ions near the RNA surface and the strength of RNA-Water interactions tend to decrease with the temperature rise. Thus the individual/combined effect of temperature, ions, and water decides the biological activity of the RNA genome. In conclusion, the research work successfully addressed the structural and dynamic behavior of biomolecules, peptides, and RNA, in an aqueous medium with an ionic effect, temperature effect, or both. The outcomes extend the current knowledge about the structure-function relationship and can assist in various biological applications.