Carlos Simmerling, the Marsha Laufer Endowed Professor of Physical and Quantitative Biology and Professor of Chemistry at Stony Brook University, will deliver a seminar entitled, "Dynamic recognition in protein-DNA complexes explored through MD simulations and experiments" Hosted by Yingkai Zhang.
For more information about Carlos Simmerling, click here.
Abstract: In contrast to proteins recognizing small-molecule ligands, DNA-dependent enzymes cannot rely solely on interactions in the substrate-binding site to achieve their exquisite specificity. It is widely believed that substrate recognition by such enzymes involves a series of conformational changes in the enzyme-DNA complex with sequential gates favoring cognate DNA and rejecting nonsubstrates. However, direct evidence for such mechanism is limited. We used state of the art molecular dynamics methods to explore the dynamic recognition of oxidative DNA damage by glycosylase enzymes. The resulting free energy landscapes, supported by biochemical analysis of site-directed mutants disturbing the interactions along the proposed path, show that the glycosylases selectively facilitate recognition dynamics, helping the rapidly sliding enzyme avoid full extrusion of every encountered base for interrogation. The seminar also will give a general background to simulation methods to provide context for the project results.