scholarly journals Solution structure and dynamics of the A-T tract DNA decamer duplex d(GGTAATTACC)2: implications for recognition by minor groove binding drugs

1999 ◽  
Vol 342 (1) ◽  
pp. 125-132 ◽  
Author(s):  
Clare E. BOSTOCK-SMITH ◽  
Charles A. LAUGHTON ◽  
Mark S. SEARLE
Keyword(s):  
Solution Structure ◽  
Minor Groove ◽  
Groove Width ◽  
Major Groove ◽  
Structure And Dynamics ◽  
Helical Twist ◽  
Distance Restraints ◽  
Dynamics Simulations ◽  
Stable Trajectory ◽  
Helical Parameters

The structure of the DNA decamer duplex d(GGTAATTACC)2 has been determined using NMR distance restraints and molecular dynamics simulations of 500 ps to 1 ns in aqueous solution at 300 K. Using both canonical A and canonical B starting structures [root-mean-square deviation (RMSD) 4.6 Å; 1 Å = 10-10 m], with and without experimental restraints, we show that all four simulations converge to a similar envelope of final conformations with B-like helical parameters (pairwise RMSD 1.27-2.03 Å between time-averaged structures). While the two restrained simulations reach a stable trajectory after 300-400 ps, the unrestrained trajectories take longer to equilibrate. We have analysed the dynamic aspects of these structures (sugar pucker, helical twist, roll, propeller twist and groove width) and show that the minor groove width in the AATT core of the duplex fluctuates significantly, sampling both wide and narrow conformations. The structure does not have the highly pre-organized narrow minor groove generally regarded as essential for recognition and binding by small molecules, suggesting that ligand binding carries with it a significant component of ‘induced-fit’. Our simulations show that there are significant differences in structure between the TpA step (where p = phosphate) and the ApA and ApT steps, where a large roll into the major groove at the TpA step appears to be an important factor in widening the minor groove at this position.

scholarly journals Hydration dynamics gives the distinctive brown color in the "brown ring" nitrate test

2021 ◽  
Author(s):  
Ambar Banerjee ◽  
Michael R. Coates ◽  
Michael Odelius
Keyword(s):  
Aqueous Solution ◽  
Ab Initio ◽  
Solution Structure ◽  
Ab Initio Molecular Dynamics ◽  
Ring Test ◽  
State Structure ◽  
Structure And Dynamics ◽  
Reference Methods ◽  
Ring Complex ◽  
Dynamics Simulations

The chemistry of the brown-ring test has been investigated for nearly a century. Though recent studies have focused on solid state structure determination and the measurement of spectra, mechanistic details and kinetics, the aspects of solution structure and dynamics remain unknown. From ab initio molecular dynamics simulations of the brown-ring complex in aqueous solution, we have identified that the classically established pseudo-octahedral [Fe(H2O)5(NO)]2+ complex is in equilibrium with a square-pyramidal [Fe(H2O)4(NO)]2+ complex through the exchange of one of the coordinated H2O molecules. We also find, using ab-initio multi-reference methods, that the mixture of these two complexes is what gives the distinctive brown coloration to the brown-ring test. We show that its UV-vis spectrum can be theoretically reproduced only by accounting these two species and not the [Fe(H2O)5(NO)]2+ complex alone. The energetics of the two complexes are also investigated with multi-reference methods.

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

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). </P><P> 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. </P><P> 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. </P><P> 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.

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