Our next webinar will take place via the internet on Tuesday December 14th at 11 AM EST/ 4 PM GMT. Sign up on our mailing list to receive the Zoom link!
We hope to see/hear from you all at one of our sessions or as one of the next speakers. If you are an early career scientist and would like to present your research, don't hesitate to submit an abstract today! For now, please learn more about our current speakers and their research below. We also thank the generous support from Cell Reports Physical Science, Merck, and the Royal Society of Chemistry.
Our featured speakers this week are Carolina Corrêa Giron (undergraduate student, Universidade de São Paulo, Brazil), and Akachukwu (AC) Obi (graduate student, University of Virginia, USA).
LEARN MORE ABOUT THE SPEAKERS AND THEIR TALKS BELOW
Carolina Corrêa Giron (on Twitter @CarolinaCGiron)
Biography: Carolina Corrêa Giron is a medical student from UFTM, Brazil, who is also a research student from Barroso Research Lab (USP). Her interests are basically Pediatrics, women's health, and infectious diseases, which made her pursue the research about SARS-CoV-2 biomolecular interactions. Two manuscripts have already been published addressing different molecular aspects os the host-pathogen interaction and therapeutic binders. Currently, the research focuses on the development and optimization of monoclonal antibodies against SARS-CoV-2 by biophysical simulation methods.
Title of Talk: Biomolecular interactions between SARS-CoV-2 receptor binding domain, ACE2, and monoclonal antibodies
Abstract: The SARS-CoV-2 betacoronavirus has emerged as a new threat to global health, demanding studies to elucidate its molecular mechanisms and to provide efficient strategies for both diagnosis, treatment, and prevention. By means of biophysical computational tools (Constant-pH Monte Carlo simulations and the PROCEEDpKa method), we estimated binding affinities between the viral receptor binding domain (RBD) from different variants and the human angiotensin-converting enzyme 2 (ACE2). Monoclonal antibodies (mAbs) that could stop the virus entry in the cell (80R, CR3022, m396, and F26G29) were also investigated. Electrostatic epitopes (EE) for all these binders were characterized, confirming a stronger dependency on electrostatic interactions. By the comparison of their binding features, CR3022 was found to be the most prominent binder. This macromolecule was further optimized employing a theoretical "alanine scanning" protocol. This allows us to suggest modifications that improve its binding affinity to the RBD of SARS-CoV-2. Based on such physicochemical analyses, the RBD-CR3022 affinity is increased by three substitutions: K170A, R194A, and K12E. Since the main therapeutic target for Covid-19 appears to be the interface between the RBD of the spike protein of the SARS-CoV-2 virus and its cellular receptor ACE2, we aim these outcomes can contribute to the increase of molecular knowledge of pathophysiology to help in the fight against the disease.
Akachukwu Obi (on Twitter @ac_obi)
Biography: AC is a fourth year Chemistry PhD candidate at the University of Virginia, Charlottesville, VA, USA, under the supervision of Prof. Dr. Robert J. Gilliard Jr. His research interests span various aspects of energy-relevant s- and p-block chemistry, with a focus on ligand-stabilization strategies due to carbon-based donor ligands. Outside of lab, AC enjoys watching and playing soccer, but if you get a chance, ask about his recent stints with fishing and softball.
Title of Talk: Dynamic NHC Coordination for the Stabilization of Organomagnesium Reagents
Abstract: Due to their earth abundance and biocompatibility, alkaline earth elements such as magnesium and calcium are attractive for energy relevant bond activations, in lieu of the more widely adopted noble metals, whose scarcity and toxicity can be disadvantageous. However, organoalkaline earth reagents are prone to complex ligand redistributions in solution (e.g., RMgX ⇆ R2Mg + MgX2 + oligomers; R, X = organic ligands), resulting in significant difficulties in the stabilizing highly reactive molecular species.
This research investigates the stereoelectronic influence of sterically unhindered N-heterocyclic carbenes (NHCs) on Lewis acidic magnesium centers. This strategy contrasts the widely adopted utilization of bulky polydentate anionic ligands (e.g., β-diketiminate), whose strong ionic interactions and stringent steric demands are considered critical to the kinetic stability of group 2 complexes. However, carbenes are attractive for their steric and electronic flexibility, and have been utilized in the stabilization of low coordinate and low oxidation-state s-block molecules.
The work described herein highlights the influence of bis- and tris(NHC) coordination in stabilizing neutral and cationic Grignard reagents, redox-active magnesium diazabutadienes and magnesium phosphaethynolate [RMg(OCP)] complexes. Interestingly, dynamic NHC coordination in these complexes imbue desirable attributes such as structural variations and enhanced Lewis acidity. The magnesium phosphaethynolate complexes represent rare examples of thermally stable group 2 phosphaethynolate complexes, which are soluble in aromatic hydrocarbons. These properties enabled Lewis-acid reactivity studies, including a remarkable thermal decarbonylation and P-atom abstraction reactivity, thus highlights their potential as small molecule building blocks in phosphorus chemistry.