This virtual seminar series highlights the latest developments in peptide and protein science, reaching a diverse audience that includes peptide and protein chemists, carbohydrate chemists, and chemical biologists.
In March 2025, the early career researchers presenting will be Dr Cheng Zhang at Cardiff University and Dr Aimee Boyle at the University of Bristol.
Dr Aimee Boyle
From coiled-coil peptides to proteins: effects on metal-binding
There is currently huge interest in designing metalloproteins capable of performing novel functions. However, metal-binding often causes changes in protein structure, and for catalysis such structural changes are usually essential during the course of the reaction. This means that in order to create new metallo-peptides and proteins, an understanding of how metal-binding affects peptide and protein folding, and vice versa is crucial. Untangling these effects is difficult 鈥� especially in natural proteins due to their inherent complexity and so de novo designed metalloproteins, which are simpler than their natural counterparts, can be used to explore relationships between metal-binding and protein folding.
We use de novo designed coiled-coil scaffolds to create metallo-peptides and proteins and explore the relationship between folding and binding. We have developed a metal-binding peptide, named HisAD, which is selective for certain transitional metal ions. Through a thorough exploration of this peptide scaffold we have uncovered that metal selectivity and stoichiometry are affected by the position of the binding site. Most recently, we have generated a protein based on this peptide scaffold and are currently investigating how selectivity is affected.
Dr Cheng Zhang
Design, Stability Engineering, and Formulation of an Antibody Fab Fragment
This study combines advanced computational and experimental techniques to improve the stability of antibody Fab fragments and reduce aggregation. Initially, computational design was employed to identify and stabilise flexible regions within a Fab, thereby lowering its tendency to aggregate under near鈥恘ative conditions. Subsequent work using X-ray scattering, molecular dynamics and smFRET revealed that an expanded Fab conformation exposes aggregation-prone areas, providing fresh insight into the aggregation mechanism. Further investigations showed that pH and temperature elicit distinct conformational fluctuations, while higher protein concentrations enhance thermal stability and diminish aggregation. Finally, high-resolution crystal structures alongside MD simulations across a range of pH values detailed how protonation influences Fab conformation. Collectively, these findings highlight the promise of rational design in developing more stable, aggregation-resistant Fab fragments for therapeutic applications.
In March 2025, the early career researchers presenting will be Dr Cheng Zhang at Cardiff University and Dr Aimee Boyle at the University of Bristol.
Dr Aimee Boyle
From coiled-coil peptides to proteins: effects on metal-binding
There is currently huge interest in designing metalloproteins capable of performing novel functions. However, metal-binding often causes changes in protein structure, and for catalysis such structural changes are usually essential during the course of the reaction. This means that in order to create new metallo-peptides and proteins, an understanding of how metal-binding affects peptide and protein folding, and vice versa is crucial. Untangling these effects is difficult 鈥� especially in natural proteins due to their inherent complexity and so de novo designed metalloproteins, which are simpler than their natural counterparts, can be used to explore relationships between metal-binding and protein folding.
We use de novo designed coiled-coil scaffolds to create metallo-peptides and proteins and explore the relationship between folding and binding. We have developed a metal-binding peptide, named HisAD, which is selective for certain transitional metal ions. Through a thorough exploration of this peptide scaffold we have uncovered that metal selectivity and stoichiometry are affected by the position of the binding site. Most recently, we have generated a protein based on this peptide scaffold and are currently investigating how selectivity is affected.
Dr Cheng Zhang
Design, Stability Engineering, and Formulation of an Antibody Fab Fragment
This study combines advanced computational and experimental techniques to improve the stability of antibody Fab fragments and reduce aggregation. Initially, computational design was employed to identify and stabilise flexible regions within a Fab, thereby lowering its tendency to aggregate under near鈥恘ative conditions. Subsequent work using X-ray scattering, molecular dynamics and smFRET revealed that an expanded Fab conformation exposes aggregation-prone areas, providing fresh insight into the aggregation mechanism. Further investigations showed that pH and temperature elicit distinct conformational fluctuations, while higher protein concentrations enhance thermal stability and diminish aggregation. Finally, high-resolution crystal structures alongside MD simulations across a range of pH values detailed how protonation influences Fab conformation. Collectively, these findings highlight the promise of rational design in developing more stable, aggregation-resistant Fab fragments for therapeutic applications.
