Fighting viruses with computers, right now

Estimation of Nanoparticle’s Surface Electrostatic Potential in Solution Using Acid–Base Molecular Probes. III. Experimental Hydrophobicity/Hydrophilicity and Charge Distribution of MS2 Virus Surface

“…MS2 is an icosahedral bacteriophage infecting Gram-negative bacteria (Escherichia coli) − and consisting of a protein outer layer (capsid) and encapsulated internal 3569 nucleotides long single stranded RNA genome partly bound to the capsid. − The capsid protects the genomic RNA; it consists of one maturation protein and 178 copies of the coat protein (arranged as 89 dimers), which self-organize in a shell structure forming the capsid. It is known that the diameter of the capsid is approximately 28 nm, and its thickness is about 2.5 nm.…”

Equilibrium dynamics of the pre- and post-cleavage regions of SP1 are separately shifted by the HIV-1 maturation inhibitor Bevirimat

“…All-atom molecular dynamics (MD) simulations are routinely used to probe protein-ligand and protein-protein interactions ( 28 – 30, 32 – 34 ). Molecular mechanics (MM) force fields (FF) are essential to MD simulations, and the reliability of the simulations depends heavily on the accuracy of the MM parameters adopted ( 35 ).…”

“…We recently derived from solid-state NMR (ssNMR) distance restraints a clearer picture of the binding of BVM, revealing that it is located in close proximity to the binding site of IP 6 (PDBIDs: 7R7P and 7R7Q). Here, starting from our ssNMR-derived structure, we have performed all-atom MD simulations ( 28, 28 – 30 ) and free energy calculations ( 31 ) of CTD-SP1 in complex with both BVM and IP 6 ; in total our simulations sampled over 100 µ s of chemical time (Supplementary Table 1). Similar to previous studiess ( 9, 23 ) we calculated CGENFF-derived parameters for BVM and encountered during validation of the parameters marked difference to the quantum mechanical potential energy surfaces.…”

Editorial overview: Special issue on virus structure and expression in current opinion in virology

“…The authors and their published researchers have reviewed technological and methodological advances on viral structure and expression in this current issue. The most advanced experimental techniques used to characterize virus particles and virus proteins, including cryogenic electronic microscopy and nuclear magnetic resonance, were thoroughly reviewed [ 1 , 2 ]; new developments in molecular dynamics simulation and other computational strategies to study virus structure and proteins were also described [ 3 ]; an elegant integrative approach combining experimental and computational methods to characterize at atomic-level the structures and dynamics of HIV-1 capsids were carefully shown [ 4 ]; pivotal examples of the structure and functional characterization of important targets for antiviral development against SARS-CoV 2 and flaviviruses were described [ 5 , 6 , 7 ]. Also, discoveries on giant viruses, which have recently shaken the virology community, were aborded, and revisions on important viral protein drug targets were made [ 8 , 9 ].…”

“…The implementation of accurate physical models, faster algorithms, new easy-to-use workflows, and software combined with hardware development, such as installing High-Performance Computing (HPC) infrastructures and improving GPUs, has contributed to turn MD simulation into a gold stander method to study biomolecular dynamics. Machado and Pantano [ 3 ] pointed out the recent t achievements and the yet-needed developments of MD simulation applied to study viruses’ structure and dynamics.…”