NMR-Derived Salt Bridges in Insulin Analogue: Resolving Artifactual Overbinding in Molecular Dynamics via Charge Scaling.

ABSTRACT: Salt bridges are ionic interactions that are of great importance in protein recognition. However, their structural description using X-ray crystallography or NMR may be inconclusive. Classical molecular dynamics (MD) used for the interpretation neglects electronic polarization, which results in artifactual overbinding. Here, we resolve the problem via charge scaling, which accounts for electronic polarization in a mean-field way. We study three salt bridges in insulin analogue. New NMR ensembles are generated via NOE-restrained MD using ff19SB and CHARMM36m force fields and the scaled-charge prosECCo75. Tens of μs of unrestrained MD show in a statistically converged manner that ff19SB induces a non-native salt bridge. This behavior is quantified via umbrella sampling of salt bridge dissoci

SUBMITTER: Le Nguyen NL 

PROVIDER: S-EPMC12302216 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature