Protein Induced Membrane Curvature in Coarse-Grained Simulations: Binding Interface, Insertion Depth and Lipid Spontaneous Curvature

Dynamics Simulations

AbstractThe N-terminal amphiphilic helices of proteins Epsin, Sar1p and Arf1 play a critical role in initiating membrane deformation. We present here the study of the interactions of these amphiphilic helices with the lipid membranes by combining the all-atom and coarse-grained simulations. In the all-atom simulations, we find that the amphiphilic helices of Epsin and Sar1p have a shallower insertion depth into the membrane compared to the amphiphilic helix of Arf1, but remarkably, the amphiphilic helices of Epsin and Sar1p induce higher asymmetry in the lipid packing between the two monolayers of the membrane. The insertion depth of amphiphilic helix into the membrane is determined not only by the overall hydrophobicity but also by the specific distribution of polar and non-polar residues along the helix. To directly compare their ability of deforming the membrane, we further apply coarse-grained simulations to investigate the membranes deformation under the insertion of multiple helices. Importantly, it is found that the amphiphilic helices of Epsin and Sar1p generate a larger membrane curvature than that of Arf1, in accord with the experimental results qualitatively. These findings enhance our understanding of the molecular mechanism of the protein-driven membrane remodeling.

Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix

ACS Nano ◽

10.1021/acsnano.0c05960 ◽

2020 ◽

Vol 14 (12) ◽

pp. 16919-16928

Author(s):

Alexis Belessiotis-Richards ◽

Stuart G. Higgins ◽

Mark S. P. Sansom ◽

Alfredo Alexander-Katz ◽

Molly M. Stevens

Keyword(s):

Membrane Curvature ◽

Coarse Grained ◽

Amphipathic Helix ◽

Curvature–undulation coupling as a basis for curvature sensing and generation in bilayer membranes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1605259113 ◽

2016 ◽

Vol 113 (35) ◽

pp. E5117-E5124 ◽

Cited By ~ 18

Author(s):

Ryan P. Bradley ◽

Ravi Radhakrishnan

Keyword(s):

Objective Function ◽

Protein Localization ◽

Membrane Curvature ◽

Coarse Grained ◽

Spontaneous Curvature ◽

Curvature Sensing ◽

Cooperative Process ◽

Dynamics Simulations ◽

A Site ◽

Dilute Limit

We present coarse-grained molecular dynamics simulations of the epsin N-terminal homology domain interacting with a lipid bilayer and demonstrate a rigorous theoretical formalism and analysis method for computing the induced curvature field in varying concentrations of the protein in the dilute limit. Our theory is based on the description of the height–height undulation spectrum in the presence of a curvature field. We formulated an objective function to compare the acquired undulation spectrum from the simulations to that of the theory. We recover the curvature field parameters by minimizing the objective function even in the limit where the protein-induced membrane curvature is of the same order as the amplitude due to thermal undulations. The coupling between curvature and undulations leads to significant predictions: (i) Under dilute conditions, the proteins can sense a site of spontaneous curvature at distances much larger than their size; (ii) as the density of proteins increases the coupling focuses and stabilizes the curvature field to the site of the proteins; and (iii) the mapping of the protein localization and the induction of a stable curvature is a cooperative process that can be described through a Hill function.

Effects of Cholesterol on the mechanism of fengycin, a biofungicide

10.1101/2021.08.02.454812 ◽

2021 ◽

Author(s):

Sreyoshi Sur ◽

Alan Grossfield

Keyword(s):

Mammalian Cells ◽

Primary Component ◽

Coarse Grained ◽

Fungal Cell ◽

Induced Membrane ◽

Membrane Bound ◽

Dynamics Simulations ◽

Recent Experimental Work ◽

Lateral Range

Fengycins are a class of antifungal lipopeptides synthesized by the bacteria Bacillus subtilis, commercially available as the primary component of the agricultural fungicide Serenade. They are toxic to fungi, but far less to mammalian cells. One key difference between mammalian and fungal cell membranes is the presence of cholesterol only in the former; recent experimental work showed that the presence of cholesterol reduces fengycin-induced membrane leakage. Since our previous all-atom and coarse-grained simulations suggested that aggregation of membrane-bound fengycin is central to its ability to disrupt membranes, we hypothesized that cholesterol might reduce fengycin aggregation. Here, we test this hypothesis using coarse-grained molecular dynamics simulations, with sampling enhanced via the weighted ensemble method. The results indicate that cholesterol subtly alters the size distribution for fengycin aggregates, limits the lateral range of their membrane disordering, and reduces the ability of aggregates to bend the membrane. Taken together, these phenomena may account for cholesterols' affects on fengycin activity.

Grand-Reaction Method for Simulations of Ionization Equilibria and Ion Partitioning in a Broad Range of pH and Ionic Strength

10.26434/chemrxiv.9741746.v1 ◽

2019 ◽

Author(s):

Jonas Landsgesell ◽

Oleg Rud ◽

Pascal Hebbeker ◽

Raju Lunkad ◽

Peter Košovan ◽

...

Keyword(s):

Mean Field ◽

Coarse Grained ◽

Reactive System ◽

Acid Base ◽

Buffer Solution ◽

Reaction Method ◽

Ionization Equilibria ◽

Ph Range ◽

Weak Polyelectrolytes

We introduce the grand-reaction method for coarse-grained simulations of acid-base equilibria in a system coupled to a reservoir at a given pH and concentration of added salt. It can be viewed as an extension of the constant-pH method and the reaction ensemble, combining explicit simulations of reactions within the system, and grand-canonical exchange of particles with the reservoir. Unlike the previously introduced methods, the grand-reaction method is applicable to acid-base equilibria in the whole pH range because it avoids known artifacts. However, the method is more general, and can be used for simulations of any reactive system coupled to a reservoir of a known composition. To demonstrate the advantages of the grand-reaction method, we simulated a model system: A solution of weak polyelectrolytes in equilibrium with a buffer solution. By carefully accounting for the exchange of all constituents, the method ensures that all chemical potentials are equal in the system and in the multi-component reservoir. Thus, the grand-reaction method is able to predict non-monotonic swelling of weak polyelectrolytes as a function of pH, that has been known from mean-field predictions and from experiments but has never been observed in coarse-grained simulations. Finally, we outline possible extensions and further generalizations of the method, and provide a set of guidelines to enable safe usage of the method by a broad community of users.<br><br>

Faculty Opinions recommendation of Kinetics of fragmentation and dissociation of two-strand protein filaments: Coarse-grained simulations and experiments.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726739280.793523159 ◽

2016 ◽

Author(s):

Vladimir Uversky

Keyword(s):

Coarse Grained ◽

Kinetics Of

Coarse Grained Simulations of Local Anesthetics Encapsulated into a Liposome

The Journal of Physical Chemistry B ◽

10.1021/jp909148n ◽

2010 ◽

Vol 114 (20) ◽

pp. 7009-7015 ◽

Cited By ~ 12

Author(s):

Mónica Pickholz ◽

Giovanni Giupponi

Keyword(s):

Local Anesthetics ◽

Coarse Grained ◽

Coarse-grained simulations of phase separation driven by DNA and its sensor protein cGAS

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2021.109001 ◽

2021 ◽

Vol 710 ◽

pp. 109001

Author(s):

Zhaoqian Su ◽

Kalyani Dhusia ◽

Yinghao Wu

Keyword(s):

Phase Separation ◽

Coarse Grained ◽

Sensor Protein ◽

Prediction and validation of protein intermediate states from structurally rich ensembles and coarse-grained simulations

Nature Communications ◽

10.1038/ncomms12575 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 27

Author(s):

Laura Orellana ◽

Ozge Yoluk ◽

Oliver Carrillo ◽

Modesto Orozco ◽

Erik Lindahl

Keyword(s):

Coarse Grained ◽

Intermediate States ◽

Effect of oligonucleic acid (ONA) backbone features on assembly of ONA–star polymer conjugates: a coarse-grained molecular simulation study

Soft Matter ◽

10.1039/c7sm01534h ◽

2017 ◽

Vol 13 (38) ◽

pp. 6770-6783 ◽

Cited By ~ 4

Author(s):

Joshua E. Condon ◽

Arthi Jayaraman

Keyword(s):

Molecular Simulation ◽

Simulation Study ◽

Coarse Grained ◽

Star Polymer ◽

Backbone Flexibility ◽

Polymer Architecture ◽

Polymer Conjugates ◽

Using coarse-grained simulations, we study the effect of varying oligonucleic acid (ONA) backbone flexibility, ONA charge and star polymer architecture on structure and thermodynamics of ONA–star polymer conjugates assembly.