Cited by 18Protein Structure and DynamicsAdvanced Physical and Chemical Molecular InteractionsAdvanced Mathematical Modeling in Engineering

‘Asynchronous reciprocal coupling of Martini 2.2 coarse-grained and CHARMM36 all-atom simulations in an automated multiscale framework’

Open access
López, Cesar A., Zhang, Xiaohua, Aydin, Fikret, Shrestha, Rebika, Van, Que N., Stanley, Christopher B., Carpenter, Timothy S., Nguyen, Kien +18 more·2022·Journal of Chemical Theory and Computation

Abstract

The appeal of multiscale modeling approaches is predicated on the promise of combinatorial synergy. However, this promise can only be realized when distinct scales are combined with reciprocal consistency. Here, we consider multiscale molecular dynamics (MD) simulations that combine the accuracy and macromolecular flexibility accessible to fixed-charge all-atom (AA) representations with the sampling speed accessible to reductive, coarse-grained (CG) representations. AA-to-CG conversions are relatively straightforward because deterministic routines with unique outcomes are achievable. Conversely, CG-to-AA conversions have many solutions due to a surge in the number of degrees of freedom. While automated tools for biomolecular CG-to-AA transformation exist, we find that one popular option, called Backward, is prone to stochastic failure and the AA models that it does generate frequently have compromised protein structure and incorrect stereochemistry. Although these shortcomings can likely be circumvented by human intervention in isolated instances, automated multiscale coupling requires reliable and robust scale conversion. Here, we detail an extension to Multiscale Machine-learned Modeling Infrastructure (MuMMI), including an improved CG-to-AA conversion tool called sinceCG. This tool is reliable (∼98% weakly correlated repeat success rate), automatable (no unrecoverable hangs), and yields AA models that generally preserve protein secondary structure and maintain correct stereochemistry. We describe how the MuMMI framework identifies CG system configurations of interest, converts them to AA representations, and simulates them at the AA scale while on-the-fly analyses provide feedback to update CG parameters. Application to systems containing the peripheral membrane protein RAS and proximal components of RAF kinase on complex eight-component lipid bilayers with ∼1.5 million atoms is discussed in the context of MuMMI.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1021/acs.jctc.2c00168

Cites

144 of 144 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A number of backmapping tools optimized for Martini already exist.

    “A number of such backmapping tools, optimized for Martini, already exist (Louison et al., 2021; Vickery and Stansfeld, 2021; López et al., 2022).”

    From Molecular dynamics simulation of an entire cell (2023) · cites this paper as López et al., 2022

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
López, C. A., Zhang, X., Aydin, F., Shrestha, R., Van, Q. N., Stanley, C. B., Carpenter, T. S., Nguyen, K., Patel, L. A., Chen, D., Burns, V., Hengartner, N. W., Reddy, T. J. E., Bhatia, H., Di Natale, F., Tran, T. H., Chan, A. H., Simanshu, D. K., Nissley, D. V., Streitz, F. H., Stephen, A. G., Turbyville, T. J., Lightstone, F. C., Gnanakaran, S., Ingólfsson, H. I., & Neale, C.
Affiliations
  • Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States
  • Lawrence Livermore National Laboratory (US)
  • Frederick National Laboratory for Cancer Research (US)
  • Oak Ridge National Laboratory (US)
  • Los Alamos National Laboratory (US)
  • Computing Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, United States
Corresponding author
Neale, Chris
Venue
Journal of Chemical Theory and Computation
Published
2022-07-22
Volume
18
Issue
8
Pages
5025-5045
ISSN
  • 1549-9618 (ISSN-L)
  • 1549-9626
OpenAlex
W4286561119
Cited by
18
References
144
Citations by year
2026: 4 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 1
FWCI
1.14
Type
journal article
Language
en
Open access
Locations
  • Journal of Chemical Theory and Computation (publishedVersion)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • National Cancer Institute
  • U.S. Department of Energy
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Advanced Physical and Chemical Molecular Interactions
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Advanced Mathematical Modeling in Engineering
Keywords
multiscale molecular dynamics, CHARMM36, protein secondary structure, Ras, Raf kinase, lipid bilayers, peripheral membrane proteins
MeSH terms
Humans, Lipid Bilayers, Proteins, Protein Structure, Secondary, Molecular Dynamics Simulation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review