Per Persson
Dekan
Molecular dynamics simulations of the adsorption of an intrinsically disordered protein: Force field and water model evaluation in comparison with experiments
Författare
Summary, in English
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.
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.
Avdelning/ar
- Beräkningskemi
- eSSENCE: The e-Science Collaboration
- BECC: Biodiversity and Ecosystem services in a Changing Climate
- Centrum för miljö- och klimatvetenskap (CEC)
- LINXS - Institute of advanced Neutron and X-ray Science
Publiceringsår
2022-10
Språk
Engelska
Publikation/Tidskrift/Serie
Frontiers in Molecular Biosciences
Volym
9
Dokumenttyp
Artikel i tidskrift
Förlag
Frontiers Media S. A.
Ämne
- Theoretical Chemistry
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 2296-889X