Paper Citing NAMD - Abstract
Pietra, Francesco
Binding Pockets and Permeation Channels for Dioxygen through Cofactorless 3-Hydroxy-2-methylquinolin-4-one 2,4-Dioxygenase in Association with Its Natural Substrate, 3-Hydroxy-2-methylquinolin-4(1H)-one. A Perspective from Molecular Dynamics Simulations
CHEMISTRY & BIODIVERSITY, 11:861-871, JUN 2014
This work describes an investigation of pathways and binging pockets (BPs) for dioxygen (O-2) through the cofactorless oxygenase 3-hydroxy-2-methylquinolin-4-one 2,4-dioxygenase in complex with its natural substrate, 3-hydroxy-2-methylquinolin-4(1H)-one, in aqueous solution. The investigation tool was random-acceleration molecular dynamics (RAMD), whereby a tiny, randomly oriented external force is applied to O-2 in order to accelerate its movements. In doing that, care was taken that the external force only continues, if O-2 moves along a direction for a given period of time, otherwise the force changed direction randomly. Gates for expulsion of O-2 from the protein, which can also be taken as gates for O-2 uptake, were found throughout almost the whole external surface of the protein, alongside a variety of BPs for O-2. The most exploited gates and BPs were not found to correspond to the single gate and BP proposed previously from the examination of the static model from X-ray diffraction analysis of this system. Therefore, experimental investigations of this system that go beyond the static model are urgently needed.
