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

Molecules ◽  
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.

Design of Inhibitors for Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Enzyme of Leishmania mexicana

2020 ◽  
Vol 16 (6) ◽  
pp. 784-795
Author(s):  
Krisnna M.A. Alves ◽  
Fábio José Bonfim Cardoso ◽  
Kathia M. Honorio ◽  
Fábio A. de Molfetta
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Binding Site ◽  
Point Of View ◽  
New Drugs ◽  
Leishmania Mexicana ◽  
Receptor Complexes ◽  
Starting Point ◽  
Dynamics Simulations ◽  
Selection Of

Background:: Leishmaniosis is a neglected tropical disease and glyceraldehyde 3- phosphate dehydrogenase (GAPDH) is a key enzyme in the design of new drugs to fight this disease. Objective:: The present study aimed to evaluate potential inhibitors of GAPDH enzyme found in Leishmania mexicana (L. mexicana). Methods: A search for novel antileishmanial molecules was carried out based on similarities from the pharmacophoric point of view related to the binding site of the crystallographic enzyme using the ZINCPharmer server. The molecules selected in this screening were subjected to molecular docking and molecular dynamics simulations. Results:: Consensual analysis of the docking energy values was performed, resulting in the selection of ten compounds. These ligand-receptor complexes were visually inspected in order to analyze the main interactions and subjected to toxicophoric evaluation, culminating in the selection of three compounds, which were subsequently submitted to molecular dynamics simulations. The docking results showed that the selected compounds interacted with GAPDH from L. mexicana, especially by hydrogen bonds with Cys166, Arg249, His194, Thr167, and Thr226. From the results obtained from molecular dynamics, it was observed that one of the loop regions, corresponding to the residues 195-222, can be related to the fitting of the substrate at the binding site, assisting in the positioning and the molecular recognition via residues responsible for the catalytic activity. Conclusion:: he use of molecular modeling techniques enabled the identification of promising compounds as inhibitors of the GAPDH enzyme from L. mexicana, and the results obtained here can serve as a starting point to design new and more effective compounds than those currently available.

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

2005 ◽  
Vol 502 ◽  
pp. 51-56 ◽  
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.

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

Polymers ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document