Cardiolipin-Dependent Properties of Model Mitochondrial Membranes from Molecular Dynamics Simulations

ABSTRACTCardiolipin is a unique anionic lipid found in mitochondrial membranes where it contributes to various mitochondrial functions, including metabolism, mitochondrial membrane fusion/fission dynamics, and apoptosis. Dysregulation of cardiolipin synthesis and remodeling have also been implicated in several diseases, such as diabetes, heart disease and Barth Syndrome. Although cardiolipin’s structural and dynamic roles have been extensively studied in binary mixtures with other phospholipids, the biophysical properties of cardiolipin in ternary lipid mixtures are still not well resolved. Here, we used molecular dynamics simulations to investigate the cardiolipin-dependent properties of ternary lipid bilayer systems that mimic the major components of mitochondrial membranes. We found that changes to cardiolipin concentration only resulted in minor changes to bilayer structural features, but that the lipid diffusion was significantly affected by those alterations. We also found that cardiolipin position along the bilayer surfaces correlated to negative curvature deflections, consistent with the induction of negative curvature stress in the membrane monolayers. This work contributes to a foundational understanding of the role of CL in altering the properties in ternary lipid mixtures composed of the major mitochondrial phospholipids, providing much needed insights to help understand how cardiolipin concentration modulates the biophysical properties of mitochondrial membranes.

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Identification of the structural features of quinazoline derivatives as EGFR inhibitors using 3D-QSAR modeling, molecular docking, molecular dynamics simulations and free energy calculations

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2021.1956591 ◽

2021 ◽

pp. 1-16

Author(s):

Fangfang Wang ◽

Wei Yang ◽

Hongping Liu ◽

Bo Zhou

Keyword(s):

Molecular Dynamics ◽

Free Energy ◽

Molecular Docking ◽

Molecular Dynamics Simulations ◽

3D Qsar ◽

Structural Features ◽

Free Energy Calculations ◽

Qsar Modeling ◽

Quinazoline Derivatives ◽

Dynamics Simulations

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Cluster, Surface and Bulk Properties of ZnCd Binary Alloys: Molecular-Dynamics Simulations

Materials Science Forum ◽

10.4028/www.scientific.net/msf.502.51 ◽

2005 ◽

Vol 502 ◽

pp. 51-56 ◽

Cited By ~ 1

Author(s):

Sakir Erkoc

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Density Functional ◽

Structural Features ◽

Bulk Materials ◽

Bulk Properties ◽

Atom Clusters ◽

Dynamics Simulations ◽

Mixed Clusters ◽

Stable Structures

The structural and electronic properties of isolated neutral ZnmCdn clusters for m+n £ 3 have been investigated by performing density functional theory calculations at B3LYP level. The optimum geometries, vibrational frequencies, electronic structures, and the possible dissosiation channels of the clusters considered have been obtained. An empirical many-body potential energy function (PEF), which comprices two- and three-body atomic interactions, has been developed to investigate the structural features and energetics of ZnmCdn (m+n=3,4) microclusters. The most stable structures were found to be triangular for the three-atom clusters and tetrahedral for the four-atom clusters. On the other hand, the structural features and energetics of Znn-mCdm (n=7,8) microclusters, and Zn50, Cd50, Zn25Cd25, Zn12Cd38, and Zn38Cd12 nanoparticles have been investigated by performing molecular-dynamics computer simulations using the developed PEF. The most stable structures were found to be compact and three-dimensional for all elemental and mixed clusters. An interesting structural feature of the mixed clusters is that Zn and Cd atoms do not mix in mixed clusters, they come together almost without mixing. Surface and bulk properties of Zn, Cd, and ZnCd systems have been investigated too by performing molecular-dynamics simulations using the developed PEF. Surface reconstruction and multilayer relaxation on clean surfaces, adatom on surface, substitutional atom on surface and bulk materials, and vacancy on surface and bulk materials have been studied extensively.

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Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations

Molecules ◽

10.3390/molecules24183261 ◽

2019 ◽

Vol 24 (18) ◽

pp. 3261

Author(s):

Sousa ◽

Laurent ◽

Quéméner ◽

Mortier ◽

Questel

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Structural Features ◽

Cellular Functions ◽

Α Subunit ◽

X Ray Crystallography ◽

Receptor Complexes ◽

Protein Interfaces ◽

Dynamics Simulations ◽

Comparison Of The Results

Interleukin 15 (IL-15), a four-helix bundle cytokine, is involved in a plethora of different cellular functions and, particularly, plays a key role in the development and activation of immune responses. IL-15 forms receptor complexes by binding with IL-2Rβ- and common γ(γc)-signaling subunits, which are shared with other members of the cytokines family (IL-2 for IL-2Rβ- and all other γc- cytokines for γc). The specificity of IL-15 is brought by the non-signaling α-subunit, IL-15Rα. Here we present the results of molecular dynamics simulations carried out on four relevant forms of IL-15: its monomer, IL-15 interacting individually with IL-15Rα (IL-15/IL-15Rα), with IL-2Rβ/γc subunits (IL-15/IL-2Rβ/γc) or with its three receptors simultaneously (IL-15/IL-15Rα/IL-2Rβ/γc). Through the analyses of the various trajectories, new insights on the structural features of the interfaces are highlighted, according to the considered form. The comparison of the results with the experimental data, available from X-ray crystallography, allows, in particular, the rationalization of the importance of IL-15 key residues (e.g. Asp8, Lys10, Glu64). Furthermore, the pivotal role of water molecules in the stabilization of the various protein-protein interfaces and their H-bonds networks are underlined for each of the considered complexes.

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Insight into the Structure and Dynamics of Polymers by Neutron Scattering Combined with Atomistic Molecular Dynamics Simulations

Polymers ◽

10.3390/polym12123067 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3067

Author(s):

Arantxa Arbe ◽

Fernando Alvarez ◽

Juan Colmenero

Keyword(s):

Molecular Dynamics ◽

Neutron Scattering ◽

Molecular Dynamics Simulations ◽

Structural Features ◽

Length Scales ◽

Polymeric Systems ◽

Structure And Dynamics ◽

Dynamical Features ◽

Dynamics Simulations ◽

Insight Into

Combining neutron scattering and fully atomistic molecular dynamics simulations allows unraveling structural and dynamical features of polymer melts at different length scales, mainly in the intermolecular and monomeric range. Here we present the methodology developed by us and the results of its application during the last years in a variety of polymers. This methodology is based on two pillars: (i) both techniques cover approximately the same length and time scales and (ii) the classical van Hove formalism allows easily calculating the magnitudes measured by neutron scattering from the simulated atomic trajectories. By direct comparison with experimental results, the simulated cell is validated. Thereafter, the information of the simulations can be exploited, calculating magnitudes that are experimentally inaccessible or extending the parameters range beyond the experimental capabilities. We show how detailed microscopic insight on structural features and dynamical processes of various kinds has been gained in polymeric systems with different degrees of complexity, and how intriguing questions as the collective behavior at intermediate length scales have been faced.

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