New Publication from Haoquan Li

"Congratulations to Haoquan for his first-author JACS article! Even though he has gone on to other things since being in our group, he did a really impressive job of continuing to move this project forward and finish another really strong paper." - Prof. Simmerling

"Here, we use molecular dynamics simulations to explore the mechanism by which OGG1 discriminates between 8-oxoG and guanine along the base eversion pathway. MD results suggest an important role for kinking of the DNA by the glycosylase, which positions DNA phosphates in a way that assists lesion recognition during base eversion. The computational predictions were validated through experimental enzyme assays on phosphorothioate substrate analogs. Our simulations suggest that OGG1 distinguishes between 8-oxoG and G using their chemical dissimilarities not only at the active site, but also at earlier stages during base eversion, and this mechanism is at least partially conserved in Fpg despite lack of structural homology. The similarity also suggests that lesion recognition through multiple gating steps may be a common theme in DNA repair. Our results provide new insight into how enzymes can exploit kinetics and DNA conformational changes to probe the chemical modifications present in DNA lesions." - excerpt from the Abstract

Check out the paper here: DNA Deformation-Coupled Recognition of 8‑Oxoguanine: Conformational Kinetic Gating in Human DNA Glycosylase. Haoquan Li, Anton V. Endutkin, Christina Bergonzo, Lin Fu, Arthur Grollman, Dmitry O. Zharkov, and Carlos Simmerling, Journal of the American Chemical Society, 2017, 139 (7), 2682-2692