2 research outputs found
Probing the Stability of a β‑Hairpin Scaffold after Desolvation
Probing
the structural characteristics of biomolecular ions in
the gas phase following native mass spectrometry (nMS) is of great
interest, because noncovalent interactions, and thus native fold features,
are believed to be largely retained upon desolvation. However, the
conformation usually depends heavily on the charge state of the species
investigated. In this study, we combine transition metal ion Förster
resonance energy transfer (tmFRET) and ion mobility-mass spectrometry
(IM-MS) with molecular dynamics (MD) simulations to interrogate the
β-hairpin structure of GB1p in vacuo. Fluorescence lifetime
values and collisional cross sections suggest an unfolding of the
β-hairpin motif for higher charge states. MD simulations are
consistent with experimental constraints, yet intriguingly provide
an alternative structural interpretation: preservation of the β-hairpin
is not only predicted for 2+ but also for 4+ charged species, which
is unexpected given the substantial Coulomb repulsion for small secondary
structure scaffolds
DASH: Dynamic Attention-Based Substructure Hierarchy for Partial Charge Assignment
We present a robust and computationally efficient approach
for
assigning partial charges of atoms in molecules. The method is based
on a hierarchical tree constructed from attention values extracted
from a graph neural network (GNN), which was trained to predict atomic
partial charges from accurate quantum-mechanical (QM) calculations.
The resulting dynamic attention-based substructure hierarchy (DASH)
approach provides fast assignment of partial charges with the same
accuracy as the GNN itself, is software-independent, and can easily
be integrated in existing parametrization pipelines, as shown for
the Open force field (OpenFF). The implementation of the DASH workflow,
the final DASH tree, and the training set are available as open source/open
data from public repositories