Protein NMR Structures Refined without NOE Data

Abstract

The refinement of low-quality structures is an important challenge in protein structure prediction. Many studies have been conducted on protein structure refinement; the refinement of structures derived from NMR spectroscopy has been especially intensively studied. In this study, we generated flat-bottom distance potential instead of NOE data because NOE data have ambiguity and uncertainty. The potential was derived from distance information from given structures and prevented structural dislocation during the refinement process. A simulated annealing protocol was used to minimize the potential energy of the structure. The protocol was tested on 134 NMR structures in the Protein Data Bank (PDB) that also have X-ray structures. Among them, 50 structures were used as a training set to find the optimal “width” parameter in the flat-bottom distance potential functions. In the validation set (the other 84 structures), most of the 12 quality assessment scores of the refined structures were significantly improved (total score increased from 1.215 to 2.044). Moreover, the secondary structure similarity of the refined structure was improved over that of the original structure. Finally, we demonstrate that the combination of two energy potentials, statistical torsion angle potential (STAP) and the flat-bottom distance potential, can drive the refinement of NMR structures.

Tracking the Biological Incorporation of Exogenous Molecules into Cellulose Fibers with Non‐Radioactive Iodinated Glucose

“…Iohexol and iopamidol are two commercially available water-soluble iodinated small-molecules used as unspecific non-radioactive, non-metabolized CT imaging agents. In plant sciences, these compounds have been used to identify water and ion movement in plants, saplings and segments of Vitis vinifera L., Olea europaea L. and Laurus nobilis L. [18] and Castanea dentata (Marshall) Borkh. [19] Also, these compounds have been utilized for the spatial, in-vivo, dynamic visualization of water movement in roots [20] or conductive conduits (xylem) during tissue desiccation/rehydration, embolism resistance [21] and repair.…”

Local Protein Structure Refinement via Molecular Dynamics Simulations with locPREFMD

“…The use of restraints and targeted rebuilding of problematic residues further contributes to speeding up convergence. A related approach was also taken recently in an improved protocol for the refinement of NMR structures, where a statistical potential was combined with flat-bottom distance potentials. But, the approach taken here went further by modifying specific bond and angle terms as well using a customized CMAP potential − to limit the sampling of regions of the Ramachandran map that are considered outliers.…”

“… 19 In another study, a simulated annealing protocol was developed using a modified potential energy function combined with a statistical torsion potential to improve the quality of NMR structures. 20 The proposed methods have demonstrated success in achieving improved local structure quality as measured by MolProbity scores, but a broad application to a wide variety of models has either not been attempted or resulted in mixed success. 19 …”

“…A straightforward strategy may involve simple all-atom minimization using atomistic force fields with constraints to preserve the overall fold. , More elaborate algorithms have employed side chain repacking with or without minimization and/or molecular dynamics to target the refinement of PDB structures in the Autofix method and the refinement of computational models in GalaxyRefine . In another study, a simulated annealing protocol was developed using a modified potential energy function combined with a statistical torsion potential to improve the quality of NMR structures . The proposed methods have demonstrated success in achieving improved local structure quality as measured by MolProbity scores, but a broad application to a wide variety of models has either not been attempted or resulted in mixed success …”

“…19 In another study, a simulated annealing protocol was developed using a modified potential energy function combined with a statistical torsion potential to improve the quality of NMR structures. 20 The proposed methods have demonstrated success in achieving improved local structure quality as measured by MolProbity scores, but a broad application to a wide variety of models has either not been attempted or resulted in mixed success. 19 Here, a more elaborate protocol is presented that combines minimization, sampling via restrained molecular dynamics, and targeted rebuilding of problematic residues to significantly improve the local structural quality of virtually any given protein model.…”