scholarly journals Intriguing Role of Water in Plant Hormone Perception

2021 ◽  
Author(s):  
Chuankai Zhao ◽  
Diego Eduardo Kleiman ◽  
Diwakar Shukla
Keyword(s):  
Free Energy ◽  
Plant Growth ◽  
Binding Site ◽  
Plant Hormones ◽  
Plant Hormone ◽  
Water Molecules ◽  
Water Displacement ◽  
Dynamics Simulations ◽  
Free Energy Of Binding

Plant hormones are small molecules that regulate plant growth, development, and responses to biotic and abiotic stresses. Plant hormones are specifically recognized by the binding site of their receptors. In this work, we investigated the role of water displacement and reorganization at the binding site of plant receptors on the binding of eight classes of phytohormones (auxin, jasmonate, gibberellin, strigolactone, brassinosteroid, cytokinin, salicylic acid, and abscisic acid) using extensive molecular dynamics simulations and inhomogeneous solvation theory. Our findings demonstrated that displacement of water molecules by phytohormones contributes to free energy of binding via entropy gain and is associated with free energy barriers. Also, our results have shown that displacement of unfavorable water molecules in the binding site can be exploited in rational agrochemical design. Overall, this study uncov- ers the role of water molecules in plant hormone perception, which creates new avenues for agrochemical design to target plant growth and development.

scholarly journals New Insights into Key Determinants for Adenosine 1 Receptor Antagonists Selectivity Using Supervised Molecular Dynamics Simulations

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 732
Author(s):  
Giovanni Bolcato ◽  
Maicol Bissaro ◽  
Giuseppe Deganutti ◽  
Mattia Sturlese ◽  
Stefano Moro
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Binding Site ◽  
Adenosine Receptors ◽  
Water Molecules ◽  
Primary Interest ◽  
Receptor Antagonists ◽  
Dynamics Simulations ◽  
Structural Insights

Adenosine receptors (ARs), like many otherGprotein-coupledreceptors (GPCRs), are targets of primary interest indrug design. However, one of the main limits for the development of drugs for this class of GPCRs is the complex selectivity profile usually displayed by ligands. Numerous efforts have been madefor clarifying the selectivity of ARs, leading to the development of many ligand-based models. The structure of the AR subtype A1 (A1AR) has been recently solved, providing important structural insights. In the present work, we rationalized the selectivity profile of two selective A1AR and A2AAR antagonists, investigating their recognition trajectories obtained by Supervised Molecular Dynamics from an unbound state and monitoring the role of the water molecules in the binding site.

scholarly journals Conformational Ensembles of an Intrinsically Disordered Protein pKID with and without a KIX Domain in Explicit Solvent Investigated by All-Atom Multicanonical Molecular Dynamics

Biomolecules ◽  
2012 ◽  
Vol 2 (1) ◽  
pp. 104-121 ◽  
Author(s):  
Koji Umezawa ◽  
Jinzen Ikebe ◽  
Mitsunori Takano ◽  
Haruki Nakamura ◽  
Junichi Higo
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Binding Site ◽  
Complex Structure ◽  
Intrinsically Disordered Protein ◽  
Bound State ◽  
Conformational Ensembles ◽  
Intrinsically Disordered ◽  
Dynamics Simulations ◽  
High Flexibility

The phosphorylated kinase-inducible activation domain (pKID) adopts a helix–loop–helix structure upon binding to its partner KIX, although it is unstructured in the unbound state. The N-terminal and C-terminal regions of pKID, which adopt helices in the complex, are called, respectively, αA and αB. We performed all-atom multicanonical molecular dynamics simulations of pKID with and without KIX in explicit solvents to generate conformational ensembles. Although the unbound pKID was disordered overall, αA and αB exhibited a nascent helix propensity; the propensity of αA was stronger than that of αB, which agrees with experimental results. In the bound state, the free-energy landscape of αB involved two low free-energy fractions: native-like and non-native fractions. This result suggests that αB folds according to the induced-fit mechanism. The αB-helix direction was well aligned as in the NMR complex structure, although the αA helix exhibited high flexibility. These results also agree quantitatively with experimental observations. We have detected that the αB helix can bind to another site of KIX, to which another protein MLL also binds with the adopting helix. Consequently, MLL can facilitate pKID binding to the pKID-binding site by blocking the MLL-binding site. This also supports experimentally obtained results.

scholarly journals Ion-water coupling controls class A GPCR signal transduction pathways

2020 ◽  
Author(s):  
Neil J. Thomson ◽  
Owen N. Vickery ◽  
Callum M. Ives ◽  
Ulrich Zachariae
Keyword(s):  
Binding Site ◽  
G Protein ◽  
Signal Transmission ◽  
Water Molecules ◽  
Long Distance ◽  
Protein Binding Region ◽  
Dynamics Simulations ◽  
Key Residues ◽  
Extracellular Sodium ◽  
Communication Pathway

G-protein-coupled receptors (GPCRs) transmit signals across the cell membrane, forming the largest family of membrane proteins in humans. Most GPCRs activate through an evolutionarily conserved mechanism, which involves reorientation of helices and key residues, rearrangement of a hydrogen bonding network mediated by water molecules, and the expulsion of a sodium ion from a protonatable binding site. However, how these components interplay to engage the signal effector binding site remains elusive. Here, we applied information theory to molecular dynamics simulations of pharmaceutically important GPCRs to trace concerted conformational variations across the receptors. We discovered a conserved communication pathway that includes protein residues and cofactors and enables the exchange of information between the extracellular sodium binding site and the intracellular G-protein binding region, coupling the most highly conserved protonatable residues at long distance. Reorientation of internal water molecules was found to be essential for signal transmission along this pathway. By inhibiting protonation, sodium decoupled this connectivity, identifying the ion as a master switch that determines the receptors’ ability to move towards active conformations.

scholarly journals Auxins and Cytokinins—The Role of Subcellular Organization on Homeostasis

2018 ◽  
Vol 19 (10) ◽  
pp. 3115 ◽  
Author(s):  
Vladimír Skalický ◽  
Martin Kubeš ◽  
Richard Napier ◽  
Ondřej Novák
Keyword(s):  
Plant Growth ◽  
Growth And Development ◽  
Recent Progress ◽  
Plant Hormone ◽  
Cell Type ◽  
Plant Growth And Development ◽  
Master Regulators ◽  
Cell Type Specific ◽  
Structural Levels

Plant hormones are master regulators of plant growth and development. Better knowledge of their spatial signaling and homeostasis (transport and metabolism) on the lowest structural levels (cellular and subcellular) is therefore crucial to a better understanding of developmental processes in plants. Recent progress in phytohormone analysis at the cellular and subcellular levels has greatly improved the effectiveness of isolation protocols and the sensitivity of analytical methods. This review is mainly focused on homeostasis of two plant hormone groups, auxins and cytokinins. It will summarize and discuss their tissue- and cell-type specific distributions at the cellular and subcellular levels.

scholarly journals Dynamic Properties of Water Confined in Graphene-Based Membrane: A Classical Molecular Dynamics Simulation Study

Membranes ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 165 ◽  
Author(s):  
One-Sun Lee
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Free Energy ◽  
Graphene Sheets ◽  
Water Molecules ◽  
Energy Profile ◽  
Confined Water ◽  
Graphene Surface ◽  
Dynamics Simulations ◽  
Density Of Water

We performed molecular dynamics simulations of water molecules inside a hydrophobic membrane composed of stacked graphene sheets. By decreasing the density of water molecules inside the membrane, we observed that water molecules form a droplet through a hydrogen bond with each other in the hydrophobic environment that stacked graphene sheets create. We found that the water droplet translates as a whole body rather than a dissipate. The translational diffusion coefficient along the graphene surface increases as the number of water molecules in the droplet decreases, because the bigger water droplet has a stronger van der Waals interaction with the graphene surface that hampers the translational motion. We also observed a longer hydrogen bond lifetime as the density of water decreased, because the hydrophobic environment limits the libration motion of the water molecules. We also calculated the reorientational correlation time of the water molecules, and we found that the rotational motion of confined water inside the membrane is anisotropic and the reorientational correlation time of confined water is slower than that of bulk water. In addition, we employed steered molecular dynamics simulations for guiding the target molecule, and measured the free energy profile of water and ion penetration through the interstice between graphene sheets. The free energy profile of penetration revealed that the optimum interlayer distance for desalination is ~10 Å, where the minimum distance for water penetration is 7 Å. With a 7 Å interlayer distance between the graphene sheets, water molecules are stabilized inside the interlayer space because of the van der Waals interaction with the graphene sheets where sodium and chloride ions suffer from a 3–8 kcal/mol energy barrier for penetration. We believe that our simulation results would be a significant contribution for designing a new graphene-based membrane for desalination.

scholarly journals Thrombin-thrombomodulin interaction: energetics and potential role of water as an allosteric effector

1995 ◽  
Vol 310 (1) ◽  
pp. 49-53 ◽  
Author(s):  
R De Cristofaro ◽  
M Picozzi ◽  
E De Candia ◽  
B Rocca ◽  
R Landolfi
Keyword(s):  
Conformational Changes ◽  
Potential Role ◽  
Competitive Inhibition ◽  
Entropy Change ◽  
Bulk Water ◽  
Water Molecules ◽  
Rabbit Lung ◽  
Allosteric Effector ◽  
Free Energy Of Binding

The interaction of rabbit lung thrombomodulin (TM) and C-terminal hirudin 54-65 fragment (Hir54-65) with human alpha-thrombin were investigated by exploiting their competitive inhibition of thrombin-fibrinogen interaction. Measurements of Ki values for TM and Hir54-65 interactions with human alpha-thrombin performed over a temperature range spanning from 10 to 40 degrees C showed a constant enthalpy for both ligands. The enthalpic and entropic contributions to the free energy of binding, however, are different for TM and the hirudin peptide. The calculated values of delta H and delta S, in fact, were -47.3 +/- 2.51 kJ (-11.3 +/- 0.6 kcal)/mol and -42.7 +/- 7.9 J (-10.2 +/- 1.9 cal)/mol.K for the hirudin peptide, while being -22.9 +/- 2.09 kJ (-5.47 +/- 0.5 kcal)/mol and 102.50 +/- 6.69 J (24.5 +/- 1.6 cal)/mol.K respectively for TM binding. These findings indicate that the interaction between thrombin and Hir54-65 is largely driven by the enthalpic contribution, whereas the positive entropy change is the driving force for the formation of the thrombin-TM complex. In other experiments performed in the presence of various concentrations of either sorbitol or sucrose it could be demonstrated that the value of the equilibrium association constant for thrombin-TM interaction increases as a function of the osmotic pressure, while the thrombin-Hir54-65 interaction was not affected by the same conditions. Moreover, control experiments showed that no major conformational changes are produced on TM by osmotic pressures used in the present study. From these experiments it was calculated that roughly 35 water molecules are released into the bulk water upon TM binding. Such a phenomenon, which is likely to be responsible for the entropic change described above, indicates the relevance of hydration processes for the formation of the thrombin-TM adduct.

Synthesis and Biological Evaluation of 3,4-Dihydro-2H-benzo[b][1,4]-oxazine-2-carboxylic Acid Derivatives as Antitubercular Agents

2020 ◽  
Vol 5 (2) ◽  
pp. 138-148
Author(s):  
Macchindra S. Tambe ◽  
Sonali Gadhe ◽  
Amit Choudhari ◽  
Dhiman Sarkar ◽  
Jaiprakash N. Sangshetti ◽  
...  
Keyword(s):  
Free Energy ◽  
Carboxylic Acid ◽  
Binding Site ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Binding Modes ◽  
Bacterial Strains ◽  
Antibacterial Screening ◽  
Free Energy Of Binding

A series of side chain modified structurally diverse 3,4-dihydro-2H-benzo[b][1,4]-oxazine-2-carboxylic acid derivatives were synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral study. All the newly synthesized compounds were examined for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra. The synthesized compounds exhibited minimum inhibitory concentration (IC50) ranging from 5.98 to >30 (μg/mL) against MtbH37Ra. Among the screened compounds, compounds 5a, 5c, 5d, 5f, 5g, 5h, 5I, 5j exhibited IC50 as 10.42, 11.81, 18.79, 5.98, 19.21, 24.81 and 14.81 μg/mL, respectively. The antibacterial screening study of these compounds was conducted against four different bacteria to asses there selectivity towards MTB. The antibacterial screening of all the synthesized compounds was conducted against four bacterial strains (Gram-negative strains: E.coli and S.aureus; Gram-positive strains: P. aeruginosa and B.subtilis. The compounds 5a, 5b, 5c, 5e and 5j showed higher antibacterial activity up to 7-25 μg/mL. Furthermore, molecular docking studies revealed the binding modes of the compounds in the binding site of the good agreement with the in vitro antitubercular screening. The compounds 5a, 5c and 5f with free energy of binding lower than -9.0 Kcal/mol binds more favourably at the binding site of panC as compared to other compounds. Specifically, the compound 5f with free energy of binding -9.6 Kcal/mol is indeed found more active in docking study as well as in the in vitro antitubercular screening. These findings open the possibility for potential lead for antituberculosis chemotherapy.

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