Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ionic transport through a protein nanopore: a Coarse-Grained Molecular Dynamics Study.

ABSTRACT: The MARTINI coarse-grained (CG) force field is used to test the ability of CG models to simulate ionic transport through protein nanopores. The ionic conductivity of CG ions in solution was computed and compared with experimental results. Next, we studied the electrostatic behavior of a solvated CG lipid bilayer in salt solution under an external electric field. We showed this approach correctly describes the experimental conditions under a potential bias. Finally, we performed CG molecular dynamics simulations of the ionic transport through a protein nanopore (?-hemolysin) inserted in a lipid bilayer, under different electric fields, for 2-3 microseconds. The resulting I?-?V curve is qualitatively consistent with experiments, although the computed current is one order of magnitude smaller. Current saturation was observed for potential biases over ±350?mV. We also discuss the time to reach a stationary regime and the role of the protein flexibility in our CG simulations.

SUBMITTER: Basdevant N

PROVIDER: S-EPMC6823379 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Ionic transport through a protein nanopore: a Coarse-Grained Molecular Dynamics Study.

Basdevant Nathalie N Dessaux Delphine D Ramirez Rosa R

Scientific reports 20191031 1

The MARTINI coarse-grained (CG) force field is used to test the ability of CG models to simulate ionic transport through protein nanopores. The ionic conductivity of CG ions in solution was computed and compared with experimental results. Next, we studied the electrostatic behavior of a solvated CG lipid bilayer in salt solution under an external electric field. We showed this approach correctly describes the experimental conditions under a potential bias. Finally, we performed CG molecular dyna ...[more]

PMID: 31673049

Similar Datasets

Coarse grained molecular dynamics simulations of transmembrane protein-lipid systems.

Project description:Many biological cellular processes occur at the micro- or millisecond time scale. With traditional all-atom molecular modeling techniques it is difficult to investigate the dynamics of long time scales or large systems, such as protein aggregation or activation. Coarse graining (CG) can be used to reduce the number of degrees of freedom in such a system, and reduce the computational complexity. In this paper the first version of a coarse grained model for transmembrane proteins is presented. This model differs from other coarse grained protein models due to the introduction of a novel angle potential as well as a hydrogen bonding potential. These new potentials are used to stabilize the backbone. The model has been validated by investigating the adaptation of the hydrophobic mismatch induced by the insertion of WALP-peptides into a lipid membrane, showing that the first step in the adaptation is an increase in the membrane thickness, followed by a tilting of the peptide.

| S-EPMC2904924 | biostudies-literature

Exploring TRPC3 Interaction with Cholesterol through Coarse-Grained Molecular Dynamics Simulations.

Project description:Transient receptor potential canonical 3 (TRPC3) channel belongs to the superfamily of transient receptor potential (TRP) channels which mediate Ca2+ influx into the cell. These channels constitute essential elements of cellular signalling and have been implicated in a wide range of diseases. TRPC3 is primarily gated by lipids and its surface expression has been shown to be dependent on cholesterol, yet a comprehensive exploration of its interaction with this lipid has thus far not emerged. Here, through 80 µs of coarse-grained molecular dynamics simulations, we show that cholesterol interacts with multiple elements of the transmembrane machinery of TRPC3. Through our approach, we identify an annular binding site for cholesterol on the pre-S1 helix and a non-annular site at the interface between the voltage-sensor-like domain and pore domains. Here, cholesterol interacts with exposed polar residues and possibly acts to stabilise the domain interface.

| S-EPMC9313397 | biostudies-literature

A generic force field for protein coarse-grained molecular dynamics simulation.

Project description:Coarse-grained (CG) force fields have become promising tools for studies of protein behavior, but the balance of speed and accuracy is still a challenge in the research of protein coarse graining methodology. In this work, 20 CG beads have been designed based on the structures of amino acid residues, with which an amino acid can be represented by one or two beads, and a CG solvent model with five water molecules was adopted to ensure the consistence with the protein CG beads. The internal interactions in protein were classified according to the types of the interacting CG beads, and adequate potential functions were chosen and systematically parameterized to fit the energy distributions. The proposed CG force field has been tested on eight proteins, and each protein was simulated for 1000 ns. Even without any extra structure knowledge of the simulated proteins, the Cα root mean square deviations (RMSDs) with respect to their experimental structures are close to those of relatively short time all atom molecular dynamics simulations. However, our coarse grained force field will require further refinement to improve agreement with and persistence of native-like structures. In addition, the root mean square fluctuations (RMSFs) relative to the average structures derived from the simulations show that the conformational fluctuations of the proteins can be sampled.

| S-EPMC3509591 | biostudies-literature

Mapping Cholesterol Interaction Sites on Serotonin Transporter through Coarse-Grained Molecular Dynamics.

Project description:Serotonin transporter (SERT) modulates serotonergic signaling via re-uptake of serotonin in pre-synaptic cells. The inclusion in cholesterol-enriched membrane domains is crucial for SERT activity, suggesting a cross-talk between the protein and the sterol. Here, we develop a protocol to identify potential cholesterol interaction sites coupling statistical analysis to multi-microsecond coarse-grained molecular dynamics simulations of SERT in a previously validated raft-like membrane model. Six putative sites were found, including a putative CRAC motif on TM4 and a CARC motif on TM10. Among them, four hot-spots near regions related to ion binding, transport, and inhibition were detected. Our results encourage prospective studies to unravel mechanistic features of the transporter and related drug discovery implications.

| S-EPMC5132266 | biostudies-literature

COARSE-GRAINED MODELING OF PROTEIN UNFOLDING DYNAMICS.

Project description:We present a new dynamic elastic network model (DENM) that describes the unfolding process of a force-loaded protein. The protein interaction network and its potentials are constructed based on information of its native-state structure obtained from the Protein Data Bank, with network nodes positioned at the Cα coordinates of the protein backbone. Specifically, to mimic the unfolding process, i.e., to simulate the process of overcoming the local energy barrier on the free energy landscape with force loading, the noncovalent protein network bonds (i.e., hydrogen bonds, salt bridges, hydrophobic contacts, etc.) are broken one-by-one with a certain probability, while the strong covalent bonds along the backbone (i.e., peptide bonds, disulfide bonds, etc.) are kept intact. The jumping event from local energy minima (bonds breaking rate) are chosen according to Kramer's theory and the Bell model. Moreover, we exploit the self-similar structure of proteins at different scales to design an effective coarse-graining procedure for DENM with optimal parameter selection. The robustness of DENM is validated by coarse-grained molecular dynamics (MD) simulation against atomistic MD simulation of force-extension processes of the Fibrinogen and Titin Immunoglobulin proteins. We observe that the native structure of the proteins determines the total unfolding dynamics (including large deviations) and not just the fluctuations around the native state.

| S-EPMC4230303 | biostudies-literature

Coarse-Grained Molecular Dynamics of pH-Sensitive Lipids.

Project description:pH-sensitive lipids represent a class of lipids that can be protonated and destabilized in acidic environments, as they become positively charged in response to low-pH conditions. They can be incorporated into lipidic nanoparticles such as liposomes, which are able to change their properties and allow specific drug delivery at the acidic conditions encountered in some pathological microenvironments. In this work, we used coarse-grained molecular-dynamic simulations to study the stability of neutral and charged lipid bilayers containing POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and various kinds of ISUCA ((F)2-(imidazol-1-yl)succinic acid)-derived lipids, which can act as pH-sensitive molecules. In order to explore such systems, we used a MARTINI-derived forcefield, previously parameterized using all-atom simulation results. We calculated the average area per lipid, the second-rank order parameter and the lipid diffusion coefficient of both lipid bilayers made of pure components and mixtures of lipids in different proportions, under neutral or acidic conditions. The results show that the use of ISUCA-derived lipids disturbs the lipid bilayer structure, with the effect being particularly marked under acidic conditions. Although more-in depth studies on these systems must be carried out, these initial results are encouraging and the lipids designed in this research could be a good basis for developing new pH-sensitive liposomes.

| S-EPMC10003205 | biostudies-literature

Molecular Dynamics Scoring of Protein-Peptide Models Derived from Coarse-Grained Docking.

Project description:One of the major challenges in the computational prediction of protein-peptide complexes is the scoring of predicted models. Usually, it is very difficult to find the most accurate solutions out of the vast number of sometimes very different and potentially plausible predictions. In this work, we tested the protocol for Molecular Dynamics (MD)-based scoring of protein-peptide complex models obtained from coarse-grained (CG) docking simulations. In the first step of the scoring procedure, all models generated by CABS-dock were reconstructed starting from their original C-alpha trace representations to all-atom (AA) structures. The second step included geometry optimization of the reconstructed complexes followed by model scoring based on receptor-ligand interaction energy estimated from short MD simulations in explicit water. We used two well-known AA MD force fields, CHARMM and AMBER, and a CG MARTINI force field. Scoring results for 66 different protein-peptide complexes show that the proposed MD-based scoring approach can be used to identify protein-peptide models of high accuracy. The results also indicate that the scoring accuracy may be significantly affected by the quality of the reconstructed protein receptor structures.

| S-EPMC8197827 | biostudies-literature

Combining coarse-grained protein models with replica-exchange all-atom molecular dynamics.

Project description:We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic details, conformations derived from the CABS simulation were subjected to replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb force fields in explicit solvent. Such a combination accelerates system convergence several times in comparison with all-atom simulations starting from the extended chain conformation, demonstrated by the analysis of melting curves, the number of native-like conformations as a function of time and secondary structure propagation. The results strongly suggest that the proposed multiscale method could be an efficient and accurate tool for high-resolution studies of protein folding dynamics in larger systems.

| S-EPMC3676820 | biostudies-literature

Coarse-grained models reveal functional dynamics--II. Molecular dynamics simulation at the coarse-grained level--theories and biological applications.

Project description:Molecular dynamics (MD) simulation has remained the most indispensable tool in studying equilibrium/non-equilibrium conformational dynamics since its advent 30 years ago. With advances in spectroscopy accompanying solved biocomplexes in growing sizes, sampling their dynamics that occur at biologically interesting spatial/temporal scales becomes computationally intractable; this motivated the use of coarse-grained (CG) approaches. CG-MD models are used to study folding and conformational transitions in reduced resolution and can employ enlarged time steps due to the absence of some of the fastest motions in the system. The Boltzmann-Inversion technique, heavily used in parameterizing these models, provides a smoothed-out effective potential on which molecular conformation evolves at a faster pace thus stretching simulations into tens of microseconds. As a result, a complete catalytic cycle of HIV-1 protease or the assembly of lipid-protein mixtures could be investigated by CG-MD to gain biological insights. In this review, we survey the theories developed in recent years, which are categorized into Folding-based and Molecular-Mechanics-based. In addition, physical bases in the selection of CG beads/time-step, the choice of effective potentials, representation of solvent, and restoration of molecular representations back to their atomic details are systematically discussed.

| S-EPMC2735960 | biostudies-literature

The kinetic landscape of nucleosome assembly: A coarse-grained molecular dynamics study.

Project description:The organization of nucleosomes along the Eukaryotic genome is maintained over time despite disruptive events such as replication. During this complex process, histones and DNA can form a variety of non-canonical nucleosome conformations, but their precise molecular details and roles during nucleosome assembly remain unclear. In this study, employing coarse-grained molecular dynamics simulations and Markov state modeling, we characterized the complete kinetics of nucleosome assembly. On the nucleosome-positioning 601 DNA sequence, we observe a rich transition network among various canonical and non-canonical tetrasome, hexasome, and nucleosome conformations. A low salt environment makes nucleosomes stable, but the kinetic landscape becomes more rugged, so that the system is more likely to be trapped in off-pathway partially assembled intermediates. Finally, we find that the co-operativity between DNA bending and histone association enables positioning sequence motifs to direct the assembly process, with potential implications for the dynamic organization of nucleosomes on real genomic sequences.

| S-EPMC8345847 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data