Comparison of NMR structures refined under implicit and explicit solvents

Abstract

Refinements with atomistic molecular dynamics (MD) simulation have contributed to improving the qualities of NMR structures. In most cases, the calculations with atomistic MD simulation for NMR structures employ generalized-Born implicit solvent model (GBIS) to take into accounts solvation effects. Developments in algorithms and computational capacities have ameliorated GBIS to approximate solvation effects that explicit solvents bring about. However, the quantitative comparison of NMR structures in the latest GBIS and explicit solvents is lacking. In this study, we report the direct comparison of NMR structures that atomistic MD simulation coupled with GBIS and water molecules refined. Two model proteins, GB1 and ubiquitin, were recalculated with experimental distance and torsion angle restraints, under a series of simulated annealing time steps. Whereas the root mean square deviations of the resulting structures were apparently similar, AMBER energies, the most favored regions in Ramachandran plot, and MolProbity clash scores witnessed that GBIS-refined structures had the better geometries. The outperformance by GBIS was distinct in the structure calculations with sparse experimental restraints. We show that the superiority stemmed, at least in parts, from the inclusion of all the pairs of non-bonded interactions. The shorter computational times with GBIS than those for explicit solvents makes GBIS a powerful method for improving structural qualities particularly under the conditions that experimental restraints are insufficient. We also propose a method to separate the native-like folds from non-violating diverged structures.