@article{10.1021/acs.jcim.6c01134,
    author = {Gomez-Flores, Claudia L. and Anggara, Kelvin},
    title = {Automating Model
Building for SPM Images of Biomolecules
Using MISO},
    journal = {Journal of Chemical Information and Modeling},
    volume = {66},
    number = {16},
    pages = {10056-10069},
    year = {2026},
    month = {08},
    abstract = {Direct imaging by scanning probe microscopy (SPM) at
cryogenic
temperatures in ultrahigh vacuum (UHV) has enabled structural characterization
of individual biomolecules in heterogeneous systems, including glycans
and glycan-decorated biomolecules (also known as glycoconjugates).
However, interpreting SPM images into molecular structures remains
a major bottleneck, particularly for flexible biomolecules that can
adopt multiple adsorption geometries. Currently, hypothesizing, constructing,
and testing these geometries are largely performed manually, thus
limiting the data throughput of SPM-based structural analysis and
the scale of molecular systems addressable by SPM imaging technologies.
Here, we present MISO (Model building from Identity, Sequence, and
Observed location) as a workflow for generating three-dimensional
biomolecular models from user-defined hypotheses about subunit identity,
connectivity, and observed locations in SPM images. MISO produces
structures consistent with user-defined hypotheses by implementing
the quaternion estimator algorithm (QUEST) followed by biased classical
molecular dynamics (MD). When applied to existing SPM data of glycans
and glycoconjugates, MISO generated structures that were qualitatively
consistent with structures previously validated by density functional
theory (DFT) calculations. In addition, we show the use of MISO in
filtering user hypotheses as well as the scale-up potential of MISO
in building a 3D model of an unfolded glycoprotein on the surface.
These results establish MISO as a practical tool for automating molecular
model building, which helps to improve the overall throughput of SPM
image interpretation of flexible biomolecules.},
    issn = {1549-9596},
    doi = {10.1021/acs.jcim.6c01134},
    url = {https://doi.org/10.1021/acs.jcim.6c01134},
    eprint = {https://pubs.acs.org/jcisd8/article-pdf/66/16/10056/66361860/acs.jcim.6c01134.pdf},
}