Self-association features of NS1 proteins from different flaviviruses

Electrostatic Features for the Receptor Binding Domain of SARS-COV-2 Wildtype and Its Variants. Compass to the Severity of the Future Variants with the Charge-Rule

“…At the same time, it is expected that such coarse-grained (CG) simulations of biomolecules should accurately describe the electrostatic interactions and pH effects. Among possible available tools, − the FORTE ( F ast c O arse-grained p R otein–pro T ein mod E l) ,, approach was a suitable choice to fulfill all these previous issues and also due to its record of successful applications in other biophysical systems ,− (including viruses ,,,,,, ) where electrostatic interactions are quite important. This was the main computational tool used in the present work.…”

“…This possibility to treat each residue type by a different value of R i is a simple way to partially account for the nonspecific contributions from the hydrophobic effect in the model. ,, Such different radii help to both preserve the macromolecular hydrophobic moments and to guide the orientation at short separation distances. Other details, justifications, validation, pros, and cons are given elsewhere. ,,,,, In short, the full configurational energy of the system [ U ({ r k })] combining a screened Coulombic term (first term) with an LJ one (second term) is given by where { r k } are amino acid coordinates at a given configuration, z i and z j are the valences of the amino acids i and j as defined by the titration scheme, e is the elementary charge ( e = 1.602 × 10 –19 C), κ is the modified inverse Debye length, , r ij is the separation distance between beads i and j , ε 0 is the dielectric constant of the vacuum (ε 0 = 8.854 × 10 –12 C 2 /Nm 2 ), ε is the dielectric constant of the medium assumed to be equal to 78.7 to mimic an aqueous solution at temperature T equals to 298 K, ε LJ is a parameter that regulates the attractive forces in the system, ,, σ ij is given by the Lorentz–Berthelot rule from the radius of beads i and j ( R i and R j ), and N is the total number of beads. The universal value of 0.124 kJ/mol was chosen for ε LJ . ,, This should be equivalent to a Hamaker constant of ca.…”

“…For instance, a drop in pH is often used to allow the host penetration. − The influenza virus, for example, needs the low pH inside the endosomal compartment to fuse its viral membrane with the endosomal membrane to release the viral genome into the cytoplasm . Such a mechanism can also induce changes in the extracellular pH. − Flaviviruses such as the Zika virus rely on pH to control the self-association of its NS1 protein which is intimately related to virulence . Another common example is the homodimerization of the envelope protein of flaviviruses .…”

Electrostatic features for the Receptor binding domain of SARS-COV-2 wildtype and its variants. Compass to the severity of the future variants with the charge-rule

“…At the same time, it is expected that such coarse-grained (CG) simulations of biomolecules should accurately describe the electrostatic interactions and pH effects. Among possible available tools, [80][81][82] the FORTE (Fast cOarse-grained pRotein-proTein modEl) 10,21,23 approach was a suitable choice to fulfill all these previous issues and also due to its record of successful applications in other biophysical systems 67,[83][84][85] (including viruses 9,10,21,23,32,51,86 ) where electrostatic interactions are quite important. This was the main computational tool used in the present work.…”

“…[18][19][20] Flaviviruses such as the Zika virus rely on pH to control the self-association of its NS1 protein which is intimately related to virulence. 21 Another common example is the homodimerization of the envelope protein of flaviviruses. 22 Therefore, it is not a surprise that SARS-CoV-2, the virus responsible for the COVID19 pandemic, would have interesting and particular electrostatic features.…”