Paper Citing NAMD - Abstract
Pietra, Francesco
Binding Pockets and Pathways for Dioxygen through the KijD3 N-Oxygenase in Complex with Flavin Mononucleotide Cofactor and a 3-Aminoglucose Substrate: Predictions from Molecular Dynamics Simulations
CHEMISTRY & BIODIVERSITY, 11:1151-1162, AUG 2014
In this work, two protein systems, Kij3DFMNAKMO(2) and Kij3DFMNO(2), made of KijD3 N-oxygenase, flavin mononucleotide (FMN) cofactor, dTDP-3-amino-2,3,6-trideoxy-4-keto-3-methyl-D-glucose (AKM) substrate, and dioxygen (O-2), have been assembled by adding a molecule of O-2, and removing (or not) AKM, to crystal data for the Kij3DFMNAKM complex. Egress of AKM and O-2 from these systems was then investigated by applying a tiny external random force, in turn, to their center of mass in the course of molecular dynamics in explicit H2O. It turned out that the wide AKM channel, even when emptied, does not constitute the main route for O-2 egress. Other routes appear to be also viable, while various binding pockets (BPs) outside the active center are prone to trap O-2. By reversing the reasoning, these can also be considered as routes for uptake of O-2 by the protein, before or after AKM uptake, while BPs may serve as reservoirs of O-2. This shows that the small molecule O-2 is capable of permeating the protein by exploiting all nearby interstices that are created on thermal fluctuations of the protein, rather than having necessarily to look for farther, permanent channels.
