| 1. |
- Adler, Jeremy, et al.
(författare)
-
Plasma membrane topology and membrane models
- 2009
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 3:Supplement 1, s. 282a-282a
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 2. |
- Blau, Christian, et al.
(författare)
-
Gromaps: A Gromacs-Based Toolset to Analyse Density Maps Derived from Molecular Dynamics Simulations
- 2019
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 116:1, s. 4-11
-
Tidskriftsartikel (refereegranskat)abstract
- We introduce a computational toolset, named GROmaρs, to obtain and compare time-averaged density maps from molecular dynamics simulations. GROmaρs efficiently computes density maps by fast multi-Gaussian spreading of atomic densities onto a three-dimensional grid. It complements existing map-based tools by enabling spatial inspection of atomic average localization during the simulations. Most importantly, it allows the comparison between computed and reference maps (e.g., experimental) through calculation of difference maps and local and time-resolved global correlation. These comparison operations proved useful to quantitatively contrast perturbed and control simulation data sets and to examine how much biomolecular systems resemble both synthetic and experimental density maps. This was especially advantageous for multimolecule systems in which standard comparisons like RMSDs are difficult to compute. In addition, GROmaρs incorporates absolute and relative spatial free-energy estimates to provide an energetic picture of atomistic localization. This is an open-source GROMACS-based toolset, thus allowing for static or dynamic selection of atoms or even coarse-grained beads for the density calculation. Furthermore, masking of regions was implemented to speed up calculations and to facilitate the comparison with experimental maps. Beyond map comparison, GROmaρs provides a straightforward method to detect solvent cavities and average charge distribution in biomolecular systems. We employed all these functionalities to inspect the localization of lipid and water molecules in aquaporin systems, the binding of cholesterol to the G protein coupled chemokine receptor type 4, and the identification of permeation pathways through the dermicidin antimicrobial channel. Based on these examples, we anticipate a high applicability of GROmaρs for the analysis of molecular dynamics simulations and their comparison with experimentally determined densities.
|
|
| 3. |
- Choudhury, Koushik, et al.
(författare)
-
An open state of a voltage-gated sodium channel involving a p-helix and conserved pore-facing asparagine
- 2022
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 121:1, s. 11-22
-
Tidskriftsartikel (refereegranskat)abstract
- Voltage-gated sodium (Nav) channels play critical roles in propagating action potentials and otherwise manipulating ionic gradients in excitable cells. These channels open in response to membrane depolarization, selectively permeating sodium ions until rapidly inactivating. Structural characterization of the gating cycle in this channel family has proved challenging, particularly due to the transient nature of the open state. A structure from the bacterium Magnetococcus marinus Nav (NavMs) was initially proposed to be open, based on its pore diameter and voltage-sensor conformation. However, the functional annotation of this model, and the structural details of the open state, remain disputed. In this work, we used molecular modeling and simulations to test possible open-state models of NavMs. The full-length experimental structure, termed here the cc-model, was consistently dehydrated at the activation gate, indicating an inability to conduct ions. Based on a spontaneous transition observed in extended simulations, and sequence/structure comparison to other Nav channels, we built an alternative p-model featuring a helix transition and the rotation of a conserved asparagine residue into the activation gate. Pore hydration, ion permeation, and state-dependent drug binding in this model were consistent with an open functional state. This work thus offers both a functional annotation of the full-length NavMs structure and a detailed model for a stable Nav open state, with potential conservation in diverse ion-channel families.
|
|
| 4. |
- Gómez-Llobregat, Jordi, et al.
(författare)
-
Anisotropic Membrane Curvature Sensing by Amphipathic Peptides
- 2016
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 110:1, s. 197-204
-
Tidskriftsartikel (refereegranskat)abstract
- Many proteins and peptides have an intrinsic capacity to sense and induce membrane curvature, and play crucial roles for organizing and remodeling cell membranes. However, the molecular driving forces behind these processes are not well understood. Here, we describe an approach to study curvature sensing by simulating the interactions of single molecules with a buckled lipid bilayer. We analyze three amphipathic antimicrobial peptides, a class of membrane-associated molecules that specifically target and destabilize bacterial membranes, and find qualitatively different sensing characteristics that would be difficult to resolve with other methods. Our findings provide evidence for direction-dependent curvature sensing mechanisms in amphipathic peptides and challenge existing theories of hydrophobic insertion. The buckling approach is generally applicable to a wide range of curvature-sensing molecules, and our results provide strong motivation to develop new experimental methods to track position and orientation of membrane proteins.
|
|
| 5. |
- Grønberg, Christina, et al.
(författare)
-
Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport
- 2016
-
Ingår i: Biophysical Journal. - : Elsevier. - 0006-3495 .- 1542-0086. ; 111:11, s. 2417-2429
-
Tidskriftsartikel (refereegranskat)abstract
- Cu+-specific P-type ATPase membrane protein transporters regulate cellular copper levels. The lack of crystal structures in Cu+-binding states has limited our understanding of how ion entry and binding are achieved. Here, we characterize the molecular basis of Cu+ entry using molecular-dynamics simulations, structural modeling, and in vitro and in vivo functional assays. Protein structural rearrangements resulting in the exposure of positive charges to bulk solvent rather than to lipid phosphates indicate a direct molecular role of the putative docking platform in Cu+ delivery. Mutational analyses and simulations in the presence and absence of Cu+ predict that the ion-entry path involves two ion-binding sites: one transient Met148-Cys382 site and one intramembranous site formed by trigonal coordination to Cys384, Asn689, and Met717. The results reconcile earlier biochemical and x-ray absorption data and provide a molecular understanding of ion entry in Cu+-transporting P-type ATPases.
|
|
| 6. |
- Hughes, Arwel, et al.
(författare)
-
Physical Properties of Bacterial Outer Membrane Models : Neutron Reflectometry & Molecular Simulation
- 2019
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 116:6, s. 1095-1104
-
Tidskriftsartikel (refereegranskat)abstract
- The outer membrane (OM) of Gram-negative bacteria is an asymmetric bilayer having phospholipids in the inner leaflet and lipopolysaccharides in the outer leaflet. This unique asymmetry and the complex carbohydrates in lipopolysaccharides make it a daunting task to study the asymmetrical OM structure and dynamics, its interactions with OM proteins, and its roles in translocation of substrates, including antibiotics. In this study, we combine neutron reflectometry and molecular simulation to explore the physical properties of OM mimetics. There is excellent agreement between experiment and simulation, allowing experimental testing of the conclusions from simulations studies and also atomistic interpretation of the behavior of experimental model systems, such as the degree of lipid asymmetry, the lipid component (tail, head, and sugar) profiles along the bilayer normal, and lateral packing (i.e., average surface area per lipid). Therefore, the combination of both approaches provides a powerful new means to explore the biological and biophysical behavior of the bacterial OM.
|
|
| 7. |
- Högberg, Carl-Johan, et al.
(författare)
-
Effect of Local Anesthetic Lidocaine on Electrostatic Properties of a Lipid Bilayer
- 2008
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 94, s. 525-531
-
Tidskriftsartikel (refereegranskat)abstract
- The influence of local anesthetic lidocaine on electrostatic properties of a lipid membrane bilayer was studied by molecular dynamics simulations. The electrostatic dipole potential, charge densities, and orientations of the headgroup angle have been examined in presence of different amounts of charged or uncharged forms of lidocaine. Important differences of the membrane properties caused by the presence of the both forms of lidocaine are presented and discussed. Our simulations have shown that both charged and uncharged lidocaine cause almost the same increase of the dipole electrostatic potential in the middle of membrane though for different reasons. The increase, being about 90 mV for 9 mol % of lidocaine and 220 mV for 28 mol% of lidocaine, is of the size which may affect the functioning of voltage-gated ion channels.
|
|
| 8. |
|
|
| 9. |
- Karjalainen, Eeva-Liisa, et al.
(författare)
-
Toward a general method to observe the phosphate groups of phosphoenzymes with infrared spectroscopy
- 2006
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 91:6, s. 2282-2289
-
Tidskriftsartikel (refereegranskat)abstract
- A general method to study the phosphate group of phosphoenzymes with infrared difference spectroscopy by helper enzyme-induced isotope exchange was developed. This allows the selective monitoring of the phosphate P-O vibrations in large proteins, which provides detailed information on several band parameters. Here, isotopic exchange was achieved at the oxygen atoms of the catalytically important phosphate group that transiently binds to the sarcoplasmic reticulum Ca2+-ATPase (SERCA1a). [γ-18O3]ATP phosphorylated the ATPase, which produced phosphoenzyme that was initially isotopically labeled. The helper enzyme adenylate kinase regenerated the substrate ATP from ADP (added or generated upon ATP hydrolysis) with different isotopic composition than used initially. With time this produced the unlabeled phosphoenzyme. The method was tested on the ADP-insensitive phosphoenzyme state of the Ca2+-ATPase for which the vibrational frequencies of the phosphate group are known, and it was established that the helper enzyme is effective in mediating the isotope exchange process.
|
|
| 10. |
- Kim, Seonghoon, et al.
(författare)
-
Bilayer Properties of Lipid A from Various Gram-Negative Bacteria
- 2016
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 111:8, s. 1750-1760
-
Tidskriftsartikel (refereegranskat)abstract
- Lipid A is the lipid anchor of a lipopolysaccharide in the outer leaflet of the outer membrane of Gram-negative bacteria. In general, lipid A consists of two phosphorylated N-acetyl glucosamine and several acyl chains that are directly linked to the two sugars. Depending on the bacterial species and environments, the acyl chain number and length vary, and lipid A can be chemically modified with phosphoethanolamine, aminoarabinose, or glycine residues, which are key to bacterial pathogenesis. In this work, homogeneous lipid bilayers of 21 distinct lipid A types from 12 bacterial species are modeled and simulated to investigate the differences and similarities of their membrane properties. In addition, different neutralizing ion types (Ca2+, K+, and Na+) are considered to examine the ion's influence on the membrane properties. The trajectory analysis shows that (1) the area per lipid is mostly correlated to the acyl chain number, and the area per lipid increases as a function of the acyl chain number; (2) the hydrophobic thickness is mainly determined by the average acyl chain length with slight dependence on the acyl chain number, and the hydrophobic thickness generally increases with the average acyl chain length; (3) a good correlation is observed among the area per lipid, hydrophobic thickness, and acyl chain order; and (4) although the influence of neutralizing ion types on the area per lipid and hydrophobic thickness is minimal, Ca2+ stays longer on the membrane surface than K+ or Na+, consequently leading to lower lateral diffusion and a higher compressibility modulus, which agrees well with available experiments.
|
|
