Improved Parameterization of Phosphatidylinositide Lipid Headgroups for the Martini 3 Coarse Grain Force Field (original) (raw)
Related papers
A systematic method to derive force fields for coarse-grained simulations of phospholipids
Computer Physics Communications, 2006
A general method to derive effective force fields for the simulation of coarse-grained versions of phospholipids is presented. The specific case of the dimyristoylphosphatidylcholine (DMPC) bilayers is considered in detail. It is shown that key structural properties are fairly well reproduced, improving the results obtained with other methods. In particular, we obtain rather accurate descriptions of the water-lipid interactions that mimic important hydration properties.
Coarse Grained Molecular Dynamics Simulations of Transmembrane Protein-Lipid Systems
International Journal of Molecular Sciences, 2010
DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User Agreement:
Molecular Dynamics Simulations of Phosphatidylcholine Membranes: A Comparative Force Field Study
Journal of Chemical Theory and Computation, 2012
Molecular dynamics simulations provide a route to studying the dynamics of lipid bilayers at atomistic or near atomistic resolution. Over the past 10 years or so, molecular dynamics simulations have become an established part of the biophysicist's tool kit for the study of model biological membranes. As simulation time scales move from tens to hundreds of nanoseconds and beyond, it is timely to re-evaluate the accuracy of simulation models. We describe a comparative analysis of five freely available force fields that are commonly used to model lipid bilayers. We focus our analysis on 1,2-dipalmitoyl-sn-glycero-3phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. We show that some bilayer properties have a pronounced force field dependence, while others are less sensitive. In general, we find strengths and weaknesses, with respect to experimental data, in all of the force fields we have studied. We do, however, find some combinations of simulation and force field parameters that should be avoided when simulating DPPC and POPC membranes. We anticipate that the results presented for some of the membrane properties will guide future improvements for several force fields studied in this work.
Simulations of Phospholipids Using a Coarse Grain Model
The Journal of Physical Chemistry B, 2001
A computationally efficient coarse grain model designed to closely mimic specific phospholipids is used to study a number of phospholipid systems to demonstrate its strengths and weaknesses. A study of a membrane containing an anesthetic, halothane, illustrates the shortcomings of this model in treating systems without extensive parametrization. In contrast, the power of the model is demonstrated by its ability to successfully simulate the self-assembly of two phospholipid phases from random initial configurations: a lamellar phase and a reverse hexagonal phase in a ternary system containing water, a hydrocarbon, and a phospholipid. The aqueous columns in the reverse hexagonal phase tend to adopt polygonal cross sections and the local structure of phospholipids is still bilayer-like. Molecular dynamics was found to be much more efficient at simulating self-assembly in the current systems than Monte Carlo.
Biophysical Journal, 2000
This report addresses the following problems associated with the generation of computer models of phospholipid bilayer membranes using molecular dynamics simulations: arbitrary initial structures and short equilibration periods, an Ewald-induced strong coupling of phospholipids, uncertainty regarding which value should be used for surface tension to alleviate the problem of the small size of the membrane, and simultaneous realization of both order parameters and the surface area. We generated a computer model of the liquid-crystalline L-␣-dimyristoylphosphatidylcholine (DMPC) bilayer, starting from a configuration based on a crystal structure (rather than from an arbitrary structure). To break the crystalline structure, a 20-ps high-temperature pulse of 510 K (but not 450 or 480 K) was effective. The system finally obtained is an all-atom model, with Ewald summation to evaluate Coulombic interactions and a constant surface tension of 35 dynes/cm/ water-membrane interface, equilibrated for 12 ns (over 50 ns total calculation time), which reproduces all of the experimentally observed parameters examined in this work. Furthermore, this model shows the presence of significant orientational correlations between neighboring alkyl chains and between shoulder vectors (which show the orientations of the lipids about their long axes) of neighboring DMPCs.
Biophysical Journal, 2011
As new atomic structures of membrane proteins are resolved, they reveal increasingly complex transmembrane topologies and highly irregular surfaces with crevices and pores. In many cases, specific interactions formed with the lipid membrane are functionally crucial, as is the overall lipid composition. Compounded with increasing protein size, these characteristics pose a challenge for the construction of simulation models of membrane proteins in lipid environments; clearly, that these models are sufficiently realistic bears upon the reliability of simulation-based studies of these systems. Here, we introduce GRIFFIN (GRIdbased Force Field INput), which uses a versatile framework to automate and improve a widely used membrane-embedding protocol. Initially, GRIFFIN carves out lipid and water molecules from a volume equivalent to that of the protein, to conserve the system density. In the subsequent optimization phase GRIFFIN adds an implicit grid-based protein force field to a molecular dynamics simulation of the precarved membrane. In this force field, atoms inside the implicit protein volume experience an outward force that will expel them from that volume, whereas those outside are subject to electrostatic and van der Waals interactions with the implicit protein. At each step of the simulation, these forces are updated by GRIFFIN and combined with the intermolecular forces of the explicit lipid-water system. This procedure enables the construction of realistic and reproducible starting configurations of the protein-membrane interface within a reasonable time frame and with minimal intervention. GRIFFIN is a stand-alone tool designed to work alongside any existing molecular dynamics package, such as NAMD or GROMACS.
The Journal of chemical physics, 2015
The architecture of a biological membrane hinges upon the fundamental fact that its properties are determined by more than the sum of its individual components. Studies on model membranes have shown the need to characterize in molecular detail how properties such as thickness, fluidity, and macroscopic bending rigidity are regulated by the interactions between individual molecules in a non-trivial fashion. Simulation-based approaches are invaluable to this purpose but are typically limited to short sampling times and model systems that are often smaller than the required properties. To alleviate both limitations, the use of coarse-grained (CG) models is nowadays an established computational strategy. We here present a new CG force field for cholesterol, which was developed by using measured properties of small molecules, and can be used in combination with our previously developed force field for phospholipids. The new model performs with precision comparable to atomistic force fiel...
Journal of Physics Condensed Matter, 2006
We have reparameterized the dihedral parameters in a commonly used unitedatom lipid force field so that they can be used with the all-atom OPLS force field for proteins implemented in the molecular dynamics simulation software GROMACS. Simulations with this new combination give stable trajectories and sensible behaviour of both lipids and protein. We have calculated the free energy of transfer of amino acid side chains between water and 'lipidcyclohexane', made of lipid force field methylene groups, as a hydrophobic mimic of the membrane interior, for both the OPLS-AA and a modified OPLS-AA force field which gives better hydration free energies under simulation conditions close to those preferred for the lipid force field. The average error is 4.3 kJ mol −1 for water-'lipid-cyclohexane' compared to 3.2 kJ mol −1 for OPLS-AA cyclohexane and 2.4 kJ mol −1 for the modified OPLS-AA water-'lipid-cyclohexane'. We have also investigated the effect of different methods to combine parameters between the united-atom lipid force field and the unitedatom protein force field ffgmx. In a widely used combination, the strength of interactions between hydrocarbon lipid tails and proteins is significantly overestimated, causing a decrease in the area per lipid and an increase in lipid ordering. Using straight combination rules improves the results. Combined, we suggest that using OPLS-AA together with the united-atom lipid force field implemented in GROMACS is a reasonable approach to membrane protein simulations. We also suggest that using partial volume information and free
Annual Review of Biophysics
Cell signaling controls essentially all cellular processes. While it is often assumed that proteins are the key architects coordinating cell signaling, recent studies have shown more and more clearly that lipids are also involved in signaling processes in a number of ways. Lipids do, for instance, act as messengers, modulate membrane receptor conformation and dynamics, and control membrane receptor partitioning. Further, through structural modifications such as oxidation, the functions of lipids as part of signaling processes can be modified. In this context, in this article we discuss the understanding recently revealed by atomistic and coarse-grained computer simulations of nanoscale processes and underlying physicochemical principles related to lipids’ functions in cellular signaling.