Effects of flexibility in coarse-grained models for bovine serum albumin and immunoglobulin G
(2023) In Journal of Chemical Physics 158(8).- Abstract
We construct a coarse-grained, structure-based, low-resolution, 6-bead flexible model of bovine serum albumin (BSA, PDB: 4F5S), which is a popular example of a globular protein in biophysical research. The model is obtained via direct Boltzmann inversion using all-atom simulations of a single molecule, and its particular form is selected from a large pool of 6-bead coarse-grained models using two suitable metrics that quantify the agreement in the distribution of collective coordinates between all-atom and coarse-grained Brownian dynamics simulations of solutions in the dilute limit. For immunoglobulin G (IgG), a similar structure-based 12-bead model has been introduced in the literature [Chaudhri et al., J. Phys. Chem. B 116, 8045... (More)
We construct a coarse-grained, structure-based, low-resolution, 6-bead flexible model of bovine serum albumin (BSA, PDB: 4F5S), which is a popular example of a globular protein in biophysical research. The model is obtained via direct Boltzmann inversion using all-atom simulations of a single molecule, and its particular form is selected from a large pool of 6-bead coarse-grained models using two suitable metrics that quantify the agreement in the distribution of collective coordinates between all-atom and coarse-grained Brownian dynamics simulations of solutions in the dilute limit. For immunoglobulin G (IgG), a similar structure-based 12-bead model has been introduced in the literature [Chaudhri et al., J. Phys. Chem. B 116, 8045 (2012)] and is employed here to compare findings for the compact BSA molecule and the more anisotropic IgG molecule. We define several modified coarse-grained models of BSA and IgG, which differ in their internal constraints and thus account for a variation of flexibility. We study denser solutions of the coarse-grained models with purely repulsive molecules (achievable by suitable salt conditions) and address the effect of packing and flexibility on dynamic and static behavior. Translational and rotational self-diffusivity is enhanced for more elastic models. Finally, we discuss a number of effective sphere sizes for the BSA molecule, which can be defined from its static and dynamic properties. Here, it is found that the effective sphere diameters lie between 4.9 and 6.1 nm, corresponding to a relative spread of about ±10% around a mean of 5.5 nm.
(Less)
- author
- Hirschmann, Frank ; Lopez, Hender ; Roosen-Runge, Felix LU ; Seydel, Tilo ; Schreiber, Frank and Oettel, Martin
- publishing date
- 2023-02-28
- type
- Contribution to journal
- publication status
- published
- in
- Journal of Chemical Physics
- volume
- 158
- issue
- 8
- article number
- 084112
- pages
- 19 pages
- publisher
- American Institute of Physics (AIP)
- external identifiers
-
- pmid:36859072
- scopus:85149269239
- ISSN
- 0021-9606
- DOI
- 10.1063/5.0132493
- language
- English
- LU publication?
- no
- id
- 6971b060-eb4d-42a1-99d6-4f893a7b40b1
- date added to LUP
- 2023-08-14 10:27:05
- date last changed
- 2024-04-20 00:30:47
@article{6971b060-eb4d-42a1-99d6-4f893a7b40b1,
abstract = {{<p>We construct a coarse-grained, structure-based, low-resolution, 6-bead flexible model of bovine serum albumin (BSA, PDB: 4F5S), which is a popular example of a globular protein in biophysical research. The model is obtained via direct Boltzmann inversion using all-atom simulations of a single molecule, and its particular form is selected from a large pool of 6-bead coarse-grained models using two suitable metrics that quantify the agreement in the distribution of collective coordinates between all-atom and coarse-grained Brownian dynamics simulations of solutions in the dilute limit. For immunoglobulin G (IgG), a similar structure-based 12-bead model has been introduced in the literature [Chaudhri et al., J. Phys. Chem. B 116, 8045 (2012)] and is employed here to compare findings for the compact BSA molecule and the more anisotropic IgG molecule. We define several modified coarse-grained models of BSA and IgG, which differ in their internal constraints and thus account for a variation of flexibility. We study denser solutions of the coarse-grained models with purely repulsive molecules (achievable by suitable salt conditions) and address the effect of packing and flexibility on dynamic and static behavior. Translational and rotational self-diffusivity is enhanced for more elastic models. Finally, we discuss a number of effective sphere sizes for the BSA molecule, which can be defined from its static and dynamic properties. Here, it is found that the effective sphere diameters lie between 4.9 and 6.1 nm, corresponding to a relative spread of about ±10% around a mean of 5.5 nm.</p>}},
author = {{Hirschmann, Frank and Lopez, Hender and Roosen-Runge, Felix and Seydel, Tilo and Schreiber, Frank and Oettel, Martin}},
issn = {{0021-9606}},
language = {{eng}},
month = {{02}},
number = {{8}},
publisher = {{American Institute of Physics (AIP)}},
series = {{Journal of Chemical Physics}},
title = {{Effects of flexibility in coarse-grained models for bovine serum albumin and immunoglobulin G}},
url = {{http://dx.doi.org/10.1063/5.0132493}},
doi = {{10.1063/5.0132493}},
volume = {{158}},
year = {{2023}},
}