TY - JOUR
AU - William Van Patten
AU - Robert Walder
AU - Ayush Adhikari
AU - Stephen Okoniewski
AU - Rashmi Ravichandran
AU - Christine Tinberg
AU - David Baker
AU - Thomas Perkins
AB - In summary, we developed an enhanced constant‐force AFM‐based assay to provide an expanded description of the free‐energy landscape underlying protein–ligand interactions. We demonstrated it by characterizing a computationally designed protein–ligand interaction and applying a more sophisticated analysis to yield ΔG≠ and the shape of the energy barrier at the transition state in addition to the traditional parameters (koff and Δx≠). By doing so in an automated and relatively rapid manner (≈2 days), we anticipate this assay will provide a more complete energy landscape description of diverse natural protein–ligand interactions as well as experimental feedback to further optimize computationally designed interactions. In turn, enhanced computationally designed protein–ligand interactions offer promising capabilities in diagnostics and therapeutics. Finally, our improved AFM‐based assay is not limited to protein–ligand interactions but can be immediately adopted to studies of protein–protein interactions29 and proteins unfolding under constant force.30
BT - ChemPhysChem
DA - 2018-01
DO - 10.1002/cphc.201701147
N2 - In summary, we developed an enhanced constant‐force AFM‐based assay to provide an expanded description of the free‐energy landscape underlying protein–ligand interactions. We demonstrated it by characterizing a computationally designed protein–ligand interaction and applying a more sophisticated analysis to yield ΔG≠ and the shape of the energy barrier at the transition state in addition to the traditional parameters (koff and Δx≠). By doing so in an automated and relatively rapid manner (≈2 days), we anticipate this assay will provide a more complete energy landscape description of diverse natural protein–ligand interactions as well as experimental feedback to further optimize computationally designed interactions. In turn, enhanced computationally designed protein–ligand interactions offer promising capabilities in diagnostics and therapeutics. Finally, our improved AFM‐based assay is not limited to protein–ligand interactions but can be immediately adopted to studies of protein–protein interactions29 and proteins unfolding under constant force.30
PY - 2018
SP - 19
EP - 23
T2 - ChemPhysChem
TI - Improved free-energy landscape quantification illustrated with a computationally designed protein-ligand interaction
UR - http://doi.wiley.com/10.1002/cphc.201701147
VL - 19
ER -