Investigating the effect of Ser256 phosphorylation on gating of aquaporin-2: Molecular Dynamics study

AbstractRegulation of water transport via aquaporins is crucial for osmoregulation and water homeostasis of an organism. This transport of water is regulated either by gating or trafficking wherein AQPs are transported from intracellular storage sites to plasma membrane. It has been proposed that water movement via AQP2 is regulated by post-translational modification. We aimed to explore the structural and functional changes occurring in AQP2 due to Ser256 phosphorylation. We have carried out molecular dynamics simulations to investigate molecular basis of effect of phosphorylation on water permeability of AQP2. MD simulations show that there are mild variations in the pore sizes of different monomers of the phosphorylated and unphosphorylated AQP2. Analysis of inter and intra-monomeric interactions such as hydrogen bond, electrostatic and hydrophobic interactions has been carried out. Structures of the phosphorylated AQP2 do not show any blocking of mouth of pore of the monomers during the course of MD simulations. Further, water permeability calculations do corroborate the above finding. This molecular dynamics study suggests that phosphorylation of C-terminal Ser-256 residue of AQP2 may not be directly responsible for gating mechanism.

Molecular Basis of Iterative C–H Oxidation by TamI, a Multifunctional P450 Monooxygenase from the Tirandamycin Biosynthetic Pathway

10.26434/chemrxiv.12710159.v1 ◽

2020 ◽

Author(s):

Sean A. Newmister ◽

Kinshuk Raj Srivastava ◽

Rosa V. Espinoza ◽

Kersti Caddell Haatveit ◽

Yogan Khatri ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Basis ◽

Hydrophobic Interactions ◽

Cytochromes P450 ◽

Targeted Mutagenesis ◽

P450 Monooxygenase ◽

Bond Functionalization ◽

Biocatalysis offers an expanding and powerful strategy to construct and diversify complex molecules by C-H bond functionalization. Due to their high selectivity, enzymes have become an essential tool for C-H bond functionalization and offer complementary reactivity to small-molecule catalysts. Hemoproteins, particularly cytochromes P450, have proven effective for selective oxidation of unactivated C-H bonds. Previously, we reported the in vitro characterization of an oxidative tailoring cascade in which TamI, a multifunctional P450 functions co-dependently with the TamL flavoprotein to catalyze regio- and stereoselective hydroxylations and epoxidation to yield tirandamycin A and tirandamycin B. TamI follows a defined order including 1) C10 hydroxylation, 2) C11/C12 epoxidation, and 3) C18 hydroxylation. Here we present a structural, biochemical, and computational investigation of TamI to understand the molecular basis of its substrate binding, diverse reactivity, and specific reaction sequence. The crystal structure of TamI in complex with tirandamycin C together with molecular dynamics simulations and targeted mutagenesis suggest that hydrophobic interactions with the polyene chain of its natural substrate are critical for molecular recognition. QM/MM calculations and molecular dynamics simulations of TamI with variant substrates provided detailed information on the molecular basis of sequential reactivity, and pattern of regio- and stereo-selectivity in catalyzing the three-step oxidative cascade.

Faculty Opinions recommendation of Enhancement of hydrophobic interactions and hydrogen bond strength by cooperativity: synthesis, modeling, and molecular dynamics simulations of a congeneric series of thrombin inhibitors.

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

10.3410/f.13372988.14743099 ◽

2011 ◽

Author(s):

Martin Stahl

Keyword(s):

Molecular Dynamics ◽

Hydrogen Bond ◽

Bond Strength ◽

Hydrophobic Interactions ◽

Thrombin Inhibitors ◽

Hydrogen Bond Strength ◽

Assessing the Antimalarial Potentials of Phytochemicals: Virtual Screening, Molecular Dynamics and In-Vitro Investigations

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180604085626 ◽

2019 ◽

Vol 16 (3) ◽

pp. 291-300

Author(s):

Saumya K. Patel ◽

Mohd Athar ◽

Prakash C. Jha ◽

Vijay M. Khedkar ◽

Yogesh Jasrai ◽

...

Keyword(s):

Molecular Dynamics ◽

Structural Integrity ◽

Md Simulations ◽

Tylophora Indica ◽

Multidrug Resistance Protein 1 ◽

Receptor Complexes ◽

Resistance Protein ◽

Dynamics Simulations ◽

Stable Trajectory

Background: Combined in-silico and in-vitro approaches were adopted to investigate the antiplasmodial activity of Catharanthus roseus and Tylophora indica plant extracts as well as their isolated components (vinblastine, vincristine and tylophorine). Methods: We employed molecular docking to prioritize phytochemicals from a library of 26 compounds against Plasmodium falciparum multidrug-resistance protein 1 (PfMDR1). Furthermore, Molecular Dynamics (MD) simulations were performed for a duration of 10 ns to estimate the dynamical structural integrity of ligand-receptor complexes. Results: The retrieved bioactive compounds viz. tylophorine, vinblastin and vincristine were found to exhibit significant interacting behaviour; as validated by in-vitro studies on chloroquine sensitive (3D7) as well as chloroquine resistant (RKL9) strain. Moreover, they also displayed stable trajectory (RMSD, RMSF) and molecular properties with consistent interaction profile in molecular dynamics simulations. Conclusion: We anticipate that the retrieved phytochemicals can serve as the potential hits and presented findings would be helpful for the designing of malarial therapeutics.

Unveiling Carbon Dioxide and Ethanol Diffusion in Carbonated Water-Ethanol Mixtures by Molecular Dynamics Simulations

Molecules ◽

10.3390/molecules26061711 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1711

Author(s):

Mohamed Ahmed Khaireh ◽

Marie Angot ◽

Clara Cilindre ◽

Gérard Liger-Belair ◽

David A. Bonhommeau

Keyword(s):

Carbon Dioxide ◽

Molecular Dynamics ◽

Diffusion Coefficients ◽

Hydrodynamic Radius ◽

Md Simulations ◽

Molecular Models ◽

Experimental Values ◽

Carbon Dioxide Co2 ◽

Dynamics Simulations ◽

Apparent Disagreement

The diffusion of carbon dioxide (CO2) and ethanol (EtOH) is a fundamental transport process behind the formation and growth of CO2 bubbles in sparkling beverages and the release of organoleptic compounds at the liquid free surface. In the present study, CO2 and EtOH diffusion coefficients are computed from molecular dynamics (MD) simulations and compared with experimental values derived from the Stokes-Einstein (SE) relation on the basis of viscometry experiments and hydrodynamic radii deduced from former nuclear magnetic resonance (NMR) measurements. These diffusion coefficients steadily increase with temperature and decrease as the concentration of ethanol rises. The agreement between theory and experiment is suitable for CO2. Theoretical EtOH diffusion coefficients tend to overestimate slightly experimental values, although the agreement can be improved by changing the hydrodynamic radius used to evaluate experimental diffusion coefficients. This apparent disagreement should not rely on limitations of the MD simulations nor on the approximations made to evaluate theoretical diffusion coefficients. Improvement of the molecular models, as well as additional NMR measurements on sparkling beverages at several temperatures and ethanol concentrations, would help solve this issue.

Mechanism of stacking fault annihilation in 3C-SiC epitaxially grown on Si(001) by molecular dynamics simulations

CrystEngComm ◽

10.1039/d0ce01613f ◽

2021 ◽

Author(s):

Andrey Sarikov ◽

Anna Marzegalli ◽

Luca Barbisan ◽

Massimo Zimbone ◽

Corrado Bongiorno ◽

...

Keyword(s):

Molecular Dynamics ◽

Stacking Faults ◽

Md Simulations ◽

Stacking Fault ◽

In this work, annihilation mechanism of stacking faults (SFs) in epitaxial 3C-SiC layers grown on Si(001) substrates is studied by molecular dynamics (MD) simulations. The evolution of SFs located in...

Molecular Dynamics Simulations of Crystal Nucleation near Interfaces in Incompatible Polymer Blends

Polymers ◽

10.3390/polym13030347 ◽

2021 ◽

Vol 13 (3) ◽

pp. 347

Author(s):

Wenlin Zhang ◽

Lingyi Zou

Keyword(s):

Molecular Dynamics ◽

Polymer Blends ◽

Md Simulations ◽

Nucleation And Growth ◽

Crystal Nucleation ◽

Crystalline Order ◽

Mobile Species ◽

Deep Supercooling ◽

Crystallizable Polymer ◽

We apply molecular dynamics (MD) simulations to investigate crystal nucleation in incompatible polymer blends under deep supercooling conditions. Simulations of isothermal nucleation are performed for phase-separated blends with different degrees of incompatibility. In weakly segregated blends, slow and incompatible chains in crystallizable polymer domains can significantly hinder the crystal nucleation and growth. When a crystallizable polymer is blended with a more mobile species in interfacial regions, enhanced molecular mobility leads to the fast growth of crystalline order. However, the incubation time remains the same as that in pure samples. By inducing anisotropic alignment near the interfaces of strongly segregated blends, phase separation also promotes crystalline order to grow near interfaces between different polymer domains.

Molecular Dynamics Simulation Study of Lecithin Inhibiting Hydrate-Dissociation

Materials Science Forum ◽

10.4028/www.scientific.net/msf.890.252 ◽

2017 ◽

Vol 890 ◽

pp. 252-259

Author(s):

Le Wang ◽

Guan Cheng Jiang ◽

Xin Lin ◽

Xian Min Zhang ◽

Qi Hui Jiang

Keyword(s):

Molecular Dynamics ◽

Water Movement ◽

Simulation Analysis ◽

Mass Density ◽

Dynamics Simulation ◽

Dissociation Process ◽

Hydrate Dissociation ◽

Hydrocarbon Chains ◽

Dynamics Simulations ◽

Mass Density Profile

Molecular dynamics simulations are used to study the dissociation inhibiting mechanism of lecithin for structure I hydrates. Adsorption characteristics of lecithin and PVP (poly (N-vinylpyrrolidine)) on the hydrate surfaces were performed in the NVT ensemble at temperatures of 277K and the hydrate dissociation process were simulated in the NPT ensemble at same temperature. The results show that hydrate surfaces with lecithin is more stable than the ones with PVP for the lower potential energy. The conformation of lecithin changes constantly after the balanced state is reached while the PVP molecular dose not. Lecithin molecule has interaction with lecithin nearby and hydrocarbon-chains of lecithin molecules will form a network to prevent the diffusion of water and methane molecules, which will narrow the available space for hydrate methane and water movement. Compared with PVP-hydrate simulation, analysis results (snapshots and mass density profile) of the dissociation simulations show that lecithin-hydrate dissociates more slowly.

Molecular dynamics simulations and CD spectroscopy reveal hydration-induced unfolding of the intrinsically disordered LEA proteins COR15A and COR15B from Arabidopsis thaliana

Physical Chemistry Chemical Physics ◽

10.1039/c6cp02272c ◽

2016 ◽

Vol 18 (37) ◽

pp. 25806-25816 ◽

Cited By ~ 13

Author(s):

Carlos Navarro-Retamal ◽

Anne Bremer ◽

Jans Alzate-Morales ◽

Julio Caballero ◽

Dirk K. Hincha ◽

...

Keyword(s):

Experimental Data ◽

Molecular Dynamics ◽

Arabidopsis Thaliana ◽

Md Simulations ◽

Cd Spectroscopy ◽

Lea Proteins ◽

Intrinsically Disordered ◽

Dynamics Simulations ◽

Crowded Environment

Unfolding of intrinsically unstructured full-length LEA proteins in a differentially crowded environment can be modeled by 30 ns MD simulations in accordance with experimental data.

The gating mechanism of the bacterial mechanosensitive channel MscL revealed by molecular dynamics simulations

Channels ◽

10.4161/chan.21895 ◽

2012 ◽

Vol 6 (4) ◽

pp. 317-331 ◽

Cited By ~ 22

Author(s):

Yasuyuki Sawada ◽

Masaki Murase ◽

Masahiro Sokabe

Keyword(s):

Molecular Dynamics ◽

Mechanosensitive Channel ◽

Gating Mechanism ◽

Simulated Breathing: Application of Molecular Dynamics Simulations to Pulmonary Lung Surfactant

Symmetry ◽

10.3390/sym13071259 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1259

Author(s):

Maksymilian Dziura ◽

Basel Mansour ◽

Mitchell DiPasquale ◽

P. Charukeshi Chandrasekera ◽

James W. Gauld ◽

...

Keyword(s):

Molecular Dynamics ◽

Pulmonary Surfactant ◽

Lung Surfactant ◽

Protein Composition ◽

Md Simulations ◽

Building Blocks ◽

Future Research ◽

Total Composition ◽

Protein Components ◽

In this review, we delve into the topic of the pulmonary surfactant (PS) system, which is present in the respiratory system. The total composition of the PS has been presented and explored, from the types of cells involved in its synthesis and secretion, down to the specific building blocks used, such as the various lipid and protein components. The lipid and protein composition varies across species and between individuals, but ultimately produces a PS monolayer with the same role. As such, the composition has been investigated for the ways in which it imposes function and confers peculiar biophysical characteristics to the system as a whole. Moreover, a couple of theories/models that are associated with the functions of PS have been addressed. Finally, molecular dynamic (MD) simulations of pulmonary surfactant have been emphasized to not only showcase various group’s findings, but also to demonstrate the validity and importance that MD simulations can have in future research exploring the PS monolayer system.