Anisotropic interactions for continuum modeling of protein–membrane systems

Oppelstrup, T.; Stanton, L. G.; Tempkin, J. B.; Ozturk, T. N.; Ingólfsson, H. I.; Carpenter, T. S.

doi:10.1063/5.0237408

Title: Anisotropic interactions for continuum modeling of protein–membrane systems

Journal Article · 30 December 2024 · Journal of Chemical Physics

DOI: https://doi.org/10.1063/5.0237408 · OSTI ID:2484249

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Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
San Jose State Univ., CA (United States)

In this work, a model for anisotropic interactions between proteins and cellular membranes is proposed for large-scale continuum simulations. The framework of the model is based on dynamic density functional theory, which provides a formalism to describe the lipid densities within the membrane as continuum fields while still maintaining the fidelity of the underlying molecular interactions. Within this framework, we extend recent results to include the anisotropic effects of protein–lipid interactions. As applications, we consider two membrane proteins of biological interest: a RAS–RAF complex tethered to the membrane and a membrane embedded G protein-coupled receptor. A strong qualitative and quantitative agreement is found between the numerical results and the corresponding molecular dynamics simulations. Combining the scope of continuum level simulations with the details from molecular level particle simulations enables research into protein–membrane behaviors at a more biologically relevant scale, which crucially can also be accessed via experiment.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: National Cancer Institute (NCI); USDOE; USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 2484249

Report Number(s):: LLNL--JRNL-865310; 1099432

Journal Information:: Journal of Chemical Physics, Journal Name: Journal of Chemical Physics Journal Issue: 24 Vol. 161; ISSN 0021-9606

Publisher:: American Institute of Physics (AIP)Copyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Anisotropic interactions
Biological and medical sciences
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Dynamic density functional theory
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Proteins

Title: Anisotropic interactions for continuum modeling of protein–membrane systems

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