| Abstract
| - Nitrophorin 4 (NP4) is a heme protein that reversibly binds nitric oxide (NO), with release rates modulatedby pH change. High-resolution structures of NP4 revealed that pH changes and NO binding induce a largeconformational rearrangement in two loops that serve to protect the heme-bound NO molecule from solvent.We used extended (110 ns) molecular dynamics simulations of NP4 at pH 5 and pH 7, modeled by selectivedeprotonation of acidic groups. Conformational and dynamic changes were observed, consistent with thosefound in the crystal. Further, major solvent movement and NO escape were observed at pH 7, while theligand remained in the heme binding pocket at pH 5. As a control, we also performed molecular dynamics(MD) simulations of sperm whale myoglobin, where NO migration into the interior cavities of the proteinwas observed, consistent with previous reports. We constructed a kinetic model of ligand escape to quantitativelyrelate the microscopic rate constants to the observed rates, and tested the predictions against the experimentaldata. The results suggest that release rates of diatomic molecules from heme proteins can be varied by severalorders of magnitude through modest adjustments in geminate rebinding and gating behavior.
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