The new SARS-CoV-2 strain shows a stronger binding affinity to ACE2due to N501Y mutant

SARS-CoV-2 is a global challenge due to its ability to spread much faster than the SARS-CoV, which was attributed to the mutations in the receptor binding domain (RBD). These mutations enhanced the electrostatic interactions. Recently, a new strain is reported in the UK that includes a mutation (N501Y) in the RBD, that is possibly increasing the infection rate. Here, using Molecular Dynamics simulations (MD) and Monte Carlo (MC) sampling, we show that the N501 mutation enhanced the electrostatic interactions due to the formation of a strong hydrogen bond between SARS-CoV-2-T500 and ACE2-D355 near the mutation site. In addition, we observed that the electrostatic interactions between the SARS-CoV-2 and ACE2 in the wild type and the mutant are dominated by salt-bridges formed between SARS-CoV-2-K417 and ACE2-D30, SARS-CoV-2-K458, ACE2-E23, and SARS-CoV-2-R403 and ACE2-E37. These interactions contributed more than 40% of the total binding energies

Probing redox potential for Iron sulfur clusters in photosystem I

Photosystem I is a light-driven electron transfer device. Available X-ray crystal structure from Thermosynechococcus elongatus, showed that electron transfer pathways consist of two nearly symmetric branches of cofactors converging at the first iron sulfur cluster FX, which is followed by two terminal iron sulfur clusters FA and FB. Experiments have shown that Fx has lower oxidation potential than FA and FB, which facilitate the electron transfer reaction. Here, we use Density Functional Theory and Multi-Conformer Continuum Electrostatics to explain the differences in the midpoint Em potentials of the Fx, FA and FB clusters. Our calculations show that Fx has the lowest oxidation potential compared to FA and FB due strong pair-wise electrostatic interactions with surrounding residues. These interactions are shown to dominated by the bridging sulfurs and cysteine ligands, which may be attributed to the shorter average bond distances between the oxidized Fe ion and ligating sulfurs for FX compared to FA and FB. Moreover, the electrostatic repulsion between the 4Fe-4S clusters and the positive potential of the backbone atoms is least for FX compared to both of FA and FB. These results agree with the experimental measurements from the redox titrations of low-temperature EPR signals and of room temperature recombination kinetics

The New SARS-CoV-2 Strain Shows a Stronger Binding Affinity to ACE2 Due to N501Y Mutation

SARS-CoV-2 is a global challenge due to its ability to spread much faster than SARS-CoV, which was attributed to the mutations in the receptor binding domain (RBD). These mutations enhanced the electrostatic interactions. Recently, a new strain was reported in the UK that includes a mutation (N501Y) in the RBD, that possibly increases the infection rate. Using Molecular Dynamics simulations (MD) and Monte Carlo (MC) sampling, we showed that the N501 mutation enhances the electrostatic interactions due to the formation of a strong hydrogen bond between SARS-CoV-2-T500 and ACE2-D355 near the mutation site. In addition, we observed that the electrostatic interactions between the SARS-CoV-2 and ACE2 in the wild type and the mutant are dominated by salt-bridges formed between SARS-CoV-2-K417 and ACE2-D30, SARS-CoV-2-K458, ACE2-E23, and SARS-CoV-2-R403 and ACE2-E37. These interactions contributed more than 40 % of the total binding energies

Computational Approach for Probing Redox Potential for Iron-Sulfur Clusters in Photosystem I

SIMPLE SUMMARY: Many biological systems contain iron–sulfur clusters, which are typically found as components of electron transport proteins. Continuum electrostatic calculations were used to investigate the effect of protein environment on the redox properties of the three iron–sulfur clusters in the cyanobacterial photosystem I. Our results show a good correlation between the estimated and the measured reduction potential. Moreover, the results indicate that the low potential of F(X) is shown to be due to the interactions with the surrounding residues and ligating sulfurs. Our results will help in understanding the electron transfer reaction in photosystem I. ABSTRACT: Photosystem I is a light-driven electron transfer device. Available X-ray crystal structure from Thermosynechococcus elongatus showed that electron transfer pathways consist of two nearly symmetric branches of cofactors converging at the first iron–sulfur cluster F(X), which is followed by two terminal iron–sulfur clusters F(A) and F(B). Experiments have shown that F(X) has lower oxidation potential than F(A) and F(B), which facilitates the electron transfer reaction. Here, we use density functional theory and Multi-Conformer Continuum Electrostatics to explain the differences in the midpoint [Formula: see text] potentials of the F(X), F(A) and F(B) clusters. Our calculations show that F(X) has the lowest oxidation potential compared to F(A) and F(B) due to strong pairwise electrostatic interactions with surrounding residues. These interactions are shown to be dominated by the bridging sulfurs and cysteine ligands, which may be attributed to the shorter average bond distances between the oxidized Fe ion and ligating sulfurs for F(X) compared to F(A) and F(B). Moreover, the electrostatic repulsion between the 4Fe-4S clusters and the positive potential of the backbone atoms is lowest for F(X) compared to both F(A) and F(B.) These results agree with the experimental measurements from the redox titrations of low-temperature EPR signals and of room temperature recombination kinetics

The Delta variant mutations in the receptor binding domain of SARS-CoV-2 show enhanced electrostatic interactions with the ACE2

The mutations in the receptor binding domain (RBD) of the SARS-CoV-2 are shown to enhance its replication, transmissibility, and binding to host cells. Recently, a new strain is reported in India that includes mutations (T478K, and L452R) in the RBD, which are possibly increasing the infection rate. Here, using Molecular Mechanics (MM) and Monte Carlo (MC) sampling, we show that the mutations in the RBD of the Delta variant of SARS-CoV-2 induced conformational changes in ACE2-E37, which enhanced the electrostatic interactions by the formation of a salt-bridge with SARS-CoV-2-R403. In addition, we observed that these mutations altered the electrostatic interactions of the salt-bridge formed between the RBD-T500 and the ACE2-D355, which reduced by more than 70% compared the to the WT