Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments
Fig 1
Schematic of the molecular fragments method.
(A) Each structural constraint (e.g., a metal ion bridge or a spin-label) is present as a molecular fragment with all atomic details in the system. (B) The residue(s) in the molecular fragment (colored in red) is/are attached to the targeting residue(s) in the wild-type protein, via harmonic restraints, with their backbone atoms (N, C, O and Cα) staying on top of each other, respectively. The residue in the molecular fragment does not have interactions with its targeting residue in the wild-type protein (residue i), and the interactions between the backbone atoms of the residue in the molecular fragment and the backbone atoms of the two nearby residues in the wild-type protein (residues i-1 and i+1; embraced by red dashed lines) are also turned off. (C) During the restrained MD simulations, the interactions within each molecular fragment are evaluated accurately triggering the conformational changes of the wild-type protein, while different molecular fragments do not have interactions with one another.