Direct electrochemical production of dissolved ozone could potentially provide economic wastewater treatment and sanitation or a valuable chemical oxidant. Although Ni‐Sb‐SnO2 electrocatalysts have the highest known faradaic efficiencies for electrochemical ozone production, the activity and selectivity are not yet sufficient for commercial implementation. This work finds that co‐doping Ni and Gd increases the ozone selectivity by a factor of three over Ni alone. These findings are the first demonstration of an active dopant other than Ni in SnO2. Electrochemical and physical characterization show that trends in ozone activity are caused by chemical catalysis, not morphology effects, and that conduction band alignment is not a catalytic descriptor for the system. Selective radical quenching experiments and quantum chemistry calculations of thermodynamic energies suggest that the kinetic barriers to form solution‐phase intermediates are important for understanding the role of dopants in electrochemical ozone production.

The spike protein in the envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with the receptor Angiotensin Converting Enzyme 2 (ACE2) on the host cell to facilitate the viral uptake. Angiotensin II (Ang II) peptide, which has a naturally high affinity for ACE2, may be useful in inhibiting this interaction. In this study, we computationally designed several Ang II mutants to find a strong binding sequence to ACE2 receptor and examined the role of ligand substitution in the docking of native as well as mutant Ang II to the ACE2 receptor. The peptide in the ACE2-peptide complex was coordinated to zinc in the ACE2 cleft. Exploratory molecular dynamics (MD) simulations were used to measure the time-based stability of the native and mutant peptides and their receptor complexes. The MD-generated root-mean-square deviation (RMSD) values are mostly similar between the native and seven mutant peptides considered in this work, although the values for free peptides demonstrated higher variation, and often were higher in amplitude than peptides associated with the ACE2 complex. An observed lack of a strong secondary structure in the short peptides is attributed to the latter's greater flexibility and movement. The strongest binding energies within the ACE2-peptide complexes were observed in the native Ang II and only one of its mutant variants, suggesting ACE2 cleft is designed to provide optimal binding to the native sequence. An examination of the S1 binding site on ACE2 suggests that complex formation alone with these peptides may not be sufficient to allosterically inhibit the binding of SARS-CoV-2 spike proteins. However, it opens up the potential for utilizing AngII-ACE2 binding in the future design of molecular and supramolecular structures to prevent spike protein interaction with the receptor through creation of steric hindrance.

The Angiotensin Converting Enzyme 2 (ACE2) is a crucial regulator for the renin-angiotensin system. ACE2 converts the Angiotensin (Ang) II peptide into Ang 1-7 and thus promotes various anti-proliferative, anti-inflammatory and cardioprotective effects. In this study, we computationally designed several Ang II mutants to find a strong binding sequence to ACE2 receptor and examined the role of ligand substitution in the docking of native as well as mutant Ang II to the receptor. The peptide in the ACE2-peptide complex was coordinated to zinc (Zn) in the ACE2 cleft. The MD-generated root-mean-square deviation values were mostly similar between the native and mutant peptides considered in this work. The initial peptide-ACE2 poses were generated by molecular docking. The MD simulations used were post-processed by MM-PBSA to generate the binding free energies. All of the peptides studied here demonstrated negative binding free energies, which suggest that all the tested peptides form stable complexes with ACE2. Additionally, by examining the trends in the binding free energies calculated with different internal dielectric constants, it is evident that native Ang II and two of its variants have strongest binding to ACE2 receptor. Even though free energy measurements through classical MD simulation have certain limitations, in the absence of the availability of crystal structures of ACE2-peptide complexes, our work provides some structural insights for various Ang II analogs and how they may interact with a zinc atom within the active site of the enzyme.

The COVID-19 pandemic has generated a major interest in designing inhibitors to prevent SARS-CoV-2 binding on host cells to protect against infection. One promising approach to such research utilizes molecular dynamics simulation to identify potential inhibitors that can prevent the interaction between spike (S) protein on the virus and angiotensin converting enzyme 2 (ACE2) receptor on the host cells. In these studies, many groups have chosen to exclude the ACE2-bound zinc (Zn) ion, which is critical for its enzymatic activity. While the relatively distant location of Zn ion from the S protein binding site (S1 domain), combined with the difficulties in modeling this ion has motivated the decision of exclusion, Zn can potentially contribute to the structural stability of the entire protein, and thus, may have implications on S protein-ACE2 interaction. In this study, the authors model both the ACE2-S1 and ACE2-inhibitor (mAb) system to investigate if there are variations in structure and the readouts due to the presence of Zn ion. Although distant from the S1 or inhibitor binding region, inclusion/exclusion of Zn has statistically significant effects on the structural stability and binding free energy in these systems. In particular, the binding free energy of the ACE2-S1 and ACE2-inhibitor structures is − 3.26 and − 14.8 kcal/mol stronger, respectively, in the Zn-bound structure than in the Zn-free structures. This finding suggests that including Zn may be important in screening potentially inhibitors and may be particularly important in modeling monoclonal antibodies, which may be more sensitive to changes in antigen structure. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s10534-023-00491-z.

The COVID-19 pandemic has generated a major interest in designing inhibitors to prevent SARS-CoV-2 binding on host cells to protect against infection. One promising approach to such research utilizes molecular dynamics (MD) to identify potential inhibitors that can prevent the interaction between spike (S) protein on the virus and angiotensin converting enzyme 2 (ACE2) receptor on the host cells. In these studies, many groups have chosen to exclude a zinc (Zn) ion bound to the ACE2 molecule which is critical for enzymatic activity. While the relatively distant location of Zn ion from the S protein binding site (S1 domain), combined with the difficulties in modeling this ion have motivated the decision of exclusion, Zn can potentially contribute to the structural stability of the entire protein, and thus, may have implications on spike protein interaction. In this study, we explored the effects of excluding Zn on the structural stability and binding free energy of the ACE2-S1 protein complex. We generated two versions of an experimentally-derived structure of the ACE2-S1 protein complex: one with Zn and one without. Examining the differences between these two complexes during MD simulation, we found that the Zn-bound complex exhibited greater instability at nearly all residues except for the interacting residues, which were more stable in the Zn-bound complex. Additionally, the Zn-bound complex had a stronger binding free energy at all internal dielectric constants greater than one. Since binding free energy is often used to score inhibitors' performances, excluding Zn could potentially have implications on inhibitor selection and performance, both in the ACE2-S1 protein system and other protein complexes that include the Zn ion.