Different aspects in explaining how mutations could affect the binding mechanism of receptor binding domain of SARS-CoV-2 spike protein in interaction with ACE2.

During replication, some mutations occur in SARS-CoV-2, the causal agent of COVID-19, leading to the emergence of different variants of the virus. The mutations that accrue in different variants of the virus, influence the virus' ability to bind to human cell receptors and ability to evade the human immune system, the rate of viral transmission, and effectiveness of vaccines. Some of these mutations occur in the receptor binding domain (RBD) of the spike protein that may change the affinity of the virus for the ACE2 receptor. In this study, several in silico techniques, such as MD and SMD simulations, were used to perform comparative studies to deeply understand the effect of mutation on structural and functional details of the interaction of the spike glycoprotein of SARS-CoV-2, with the ACE2 receptor. According to our results, the mutation in the RBD associated with the Omicron variant increase binding affinity of the virus to ACE2 when compared to wild type and Delta variants. We also observed that the flexibility of the spike protein of the Omicron variant was lower than in comparison to other variants. In summary, different mutations in variants of the virus can have an effect on the binding mechanism of the receptor binding domain of the virus with ACE2.

A molecular dynamics investigation on transporting mechanism of glucose through a cyclic peptide nanotube.

Cyclic peptide nanotubes (CPNTs) are open-ended, hollow, and tubular structures that are made of several cyclic peptide rings. These structures can act as a transmembrane channel and transport ions or small molecules. In this work, we studied the stability of a cyclic peptide nanotube 8 × [(Trp-D-Leu)4-Gln-D-Leu] into a fully hydrated membrane composed of DPPC/POPC/POPS/cholesterol and also the transport mechanism of ß-D-glucose through this nanotube was investigated. Our findings revealed that the CPNT was stable in the lipid bilayer during the simulation time and non-bonded interactions, especially hydrogen bonding have an important role to form a stable CPNT in the membrane. The glucose jumps from a Cα-region into the mid-Cα region and spends more time in this region because of its more desirable interactions with water molecules and the CPNT. In the transport pathway, non-bonded interactions between glucose, water molecules and the CPNT facilitate the transport of the glucose through the CPNT. The collaboration of hydrogen bonds, electrostatic and van der Waals interactions change the pulling force and lead to transport glucose through the CPNT. Potential of mean force (PMF) calculations revealed that the glucose has a minimum value of binding free energy and maximum configurational entropy in MPR regions. These findings can be used to design more CPNTs with different goals such as drug delivery.Communicated by Ramaswamy H. Sarma.