Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Molecular dynamics simulations of the adsorption of an intrinsically disordered protein: Force field and water model evaluation in comparison with experiments

Koder Hamid, Mona LU ; Månsson, Linda K. LU ; Meklesh, Viktoriia LU ; Persson, Per LU and Skepö, Marie LU (2022) In Frontiers in Molecular Biosciences 9.
Abstract
This study investigates possible structural changes of an intrinsically
disordered protein (IDP) when it adsorbs to a solid surface. Experiments
on IDPs primarily result in ensemble averages due to their high
dynamics. Therefore, molecular dynamics (MD) simulations are crucial for
obtaining more detailed information on the atomistic and molecular
levels. An evaluation of seven different force field and water model
combinations have been applied: (A) CHARMM36IDPSFF + CHARMM-modified
TIP3P, (B) CHARMM36IDPSFF + TIP4P-D, (C) CHARMM36m + CHARMM-modified
TIP3P, (D) AMBER99SB-ILDN + TIP3P, (E) AMBER99SB-ILDN + TIP4P-D, (F)
AMBERff03ws + TIP4P/2005, and (G) AMBER99SB-disp + disp-water. The
results... (More)
This study investigates possible structural changes of an intrinsically
disordered protein (IDP) when it adsorbs to a solid surface. Experiments
on IDPs primarily result in ensemble averages due to their high
dynamics. Therefore, molecular dynamics (MD) simulations are crucial for
obtaining more detailed information on the atomistic and molecular
levels. An evaluation of seven different force field and water model
combinations have been applied: (A) CHARMM36IDPSFF + CHARMM-modified
TIP3P, (B) CHARMM36IDPSFF + TIP4P-D, (C) CHARMM36m + CHARMM-modified
TIP3P, (D) AMBER99SB-ILDN + TIP3P, (E) AMBER99SB-ILDN + TIP4P-D, (F)
AMBERff03ws + TIP4P/2005, and (G) AMBER99SB-disp + disp-water. The
results have been qualitatively compared with those of small-angle X-ray
scattering, synchrotron radiation circular dichroism spectroscopy, and
attenuated total reflectance Fourier transform infrared spectroscopy.
The model IDP corresponds to the first 33 amino acids of the N-terminal
of the magnesium transporter A (MgtA) and is denoted as KEIF. With a net
charge of +3, KEIF is found to adsorb to the anionic synthetic clay
mineral Laponite® due to the increase in entropy from the
concomitant release of counterions from the surface. The experimental
results show that the peptide is largely disordered with a random coil
conformation, whereas the helical content (α- and/or 310-helices)
increased upon adsorption. MD simulations corroborate these findings
and further reveal an increase in polyproline II helices and an
extension of the peptide conformation in the adsorbed state. In
addition, the simulations provided atomistic resolution of the adsorbed
ensemble of structures, where the arginine residues had a high
propensity to form hydrogen bonds with the surface. Simulations B, E,
and G showed significantly better agreement with experiments than the
other simulations. Particularly noteworthy is the discovery that B and E
with TIP4P-D water had superior performance to their corresponding
simulations A and D with TIP3P-type water. Thus, this study shows the
importance of the water model when simulating IDPs and has also provided
an insight into the structural changes of surface-active IDPs induced
by adsorption, which may play an important role in their function. (Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Frontiers in Molecular Biosciences
volume
9
article number
958175
pages
14 pages
publisher
Frontiers Media S. A.
external identifiers
  • pmid:36387274
  • scopus:85141614315
ISSN
2296-889X
DOI
10.3389/fmolb.2022.958175
language
English
LU publication?
yes
id
9802fbc9-8ead-4fe7-a2ee-69ec090f13c3
date added to LUP
2022-10-30 14:08:56
date last changed
2023-04-05 23:58:48
@article{9802fbc9-8ead-4fe7-a2ee-69ec090f13c3,
  abstract     = {{This study investigates possible structural changes of an intrinsically <br>
disordered protein (IDP) when it adsorbs to a solid surface. Experiments<br>
 on IDPs primarily result in ensemble averages due to their high <br>
dynamics. Therefore, molecular dynamics (MD) simulations are crucial for<br>
 obtaining more detailed information on the atomistic and molecular <br>
levels. An evaluation of seven different force field and water model <br>
combinations have been applied: (A) CHARMM36IDPSFF + CHARMM-modified <br>
TIP3P, (B) CHARMM36IDPSFF + TIP4P-D, (C) CHARMM36m + CHARMM-modified <br>
TIP3P, (D) AMBER99SB-ILDN + TIP3P, (E) AMBER99SB-ILDN + TIP4P-D, (F) <br>
AMBERff03ws + TIP4P/2005, and (G) AMBER99SB-disp + disp-water. The <br>
results have been qualitatively compared with those of small-angle X-ray<br>
 scattering, synchrotron radiation circular dichroism spectroscopy, and <br>
attenuated total reflectance Fourier transform infrared spectroscopy. <br>
The model IDP corresponds to the first 33 amino acids of the N-terminal <br>
of the magnesium transporter A (MgtA) and is denoted as KEIF. With a net<br>
 charge of +3, KEIF is found to adsorb to the anionic synthetic clay <br>
mineral Laponite<sup>®</sup> due to the increase in entropy from the <br>
concomitant release of counterions from the surface. The experimental <br>
results show that the peptide is largely disordered with a random coil <br>
conformation, whereas the helical content (α- and/or 3<sub>10</sub>-helices)<br>
 increased upon adsorption. MD simulations corroborate these findings <br>
and further reveal an increase in polyproline II helices and an <br>
extension of the peptide conformation in the adsorbed state. In <br>
addition, the simulations provided atomistic resolution of the adsorbed <br>
ensemble of structures, where the arginine residues had a high <br>
propensity to form hydrogen bonds with the surface. Simulations B, E, <br>
and G showed significantly better agreement with experiments than the <br>
other simulations. Particularly noteworthy is the discovery that B and E<br>
 with TIP4P-D water had superior performance to their corresponding <br>
simulations A and D with TIP3P-type water. Thus, this study shows the <br>
importance of the water model when simulating IDPs and has also provided<br>
 an insight into the structural changes of surface-active IDPs induced <br>
by adsorption, which may play an important role in their function.}},
  author       = {{Koder Hamid, Mona and Månsson, Linda K. and Meklesh, Viktoriia and Persson, Per and Skepö, Marie}},
  issn         = {{2296-889X}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Molecular Biosciences}},
  title        = {{Molecular dynamics simulations of the adsorption of an intrinsically disordered protein: Force field and water model evaluation in comparison with experiments}},
  url          = {{http://dx.doi.org/10.3389/fmolb.2022.958175}},
  doi          = {{10.3389/fmolb.2022.958175}},
  volume       = {{9}},
  year         = {{2022}},
}