Computational Studies of the Active and Inactive Regulatory Domains of Response Regulator PhoP Using Molecular Dynamics Simulations

2017 ◽  
Vol 36 (11) ◽  
pp. 1700031 ◽  
Author(s):  
Xiao‐Yu Qing ◽  
Hans Steenackers ◽  
Tom Venken ◽  
Marc De Maeyer ◽  
Arnout Voet
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Response Regulator ◽  
Computational Studies ◽  
Regulatory Domains ◽  
Dynamics Simulations

scholarly journals Molecular Basis for Spirocycle Formation in the Paraherquamide Biosynthetic Pathway

2019 ◽  
Author(s):  
Amy E. Fraley ◽  
Kersti Caddell Haatveit ◽  
Ying Ye ◽  
Samantha P. Kelly ◽  
Sean A. Newmister ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Natural Products ◽  
Molecular Dynamics Simulations ◽  
Molecular Basis ◽  
Biosynthetic Pathway ◽  
Three Dimensional ◽  
Enzymatic Reactions ◽  
Computational Studies ◽  
Penicillium Simplicissimum ◽  
Dynamics Simulations

<div> <div> <div> <p>The paraherquamides are potent anthelmintic natural products with complex heptacyclic scaffolds. One key feature of these molecules is the spiro-oxindole moiety that lends a strained three-dimensional architecture to these structures. The flavin monooxygenase PhqK was found to catalyze spirocycle formation through two parallel pathways in the biosynthesis of paraherquamides A and G. Two new paraherquamides (K and L) were isolated from a ΔphqK strain of Penicillium simplicissimum, and subsequent enzymatic reactions with these compounds generated two additional metabolites paraherquamides M and N. Crystal structures of PhqK in complex with various substrates provided a foundation for mechanistic analyses and computational studies. While it is evident that PhqK can react with various substrates, reaction kinetics and molecular dynamics simulations indicated that the dioxepin-containing paraherquamide L was the favored substrate. Through this effort, we have elucidated a key step in the biosynthesis of the paraherquamides, and provided a rationale for the selective spirocyclization of these powerful anthelmintic agents. </p></div></div><div><div> </div> </div> </div>

Computational studies on the binding mechanism between triazolone inhibitors and Chk1 by molecular docking and molecular dynamics

2015 ◽  
Vol 11 (1) ◽  
pp. 275-286 ◽  
Author(s):  
Min Lv ◽  
Shuying Ma ◽  
Yueli Tian ◽  
Xiaoyun Zhang ◽  
Wenjuan Lv ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Protein Interaction ◽  
Computational Studies ◽  
Inhibitor Protein ◽  
Binding Mechanism ◽  
Interaction Diagram ◽  
Dynamics Simulations

The 3D inhibitor–protein interaction diagram of (a) the Chk1–5a complex (ΔGpred = −45.64 kcal mol−1) and (b) the Chk1–31 complex (ΔGpred = −35.28 kcal mol−1) obtained from molecular dynamics simulations.

scholarly journals Unfolding of α-helical 20-residue poly-glutamic acid analyzed by multiple runs of canonical molecular dynamics simulations

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4769 ◽  
Author(s):  
Naoki Ogasawara ◽  
Kota Kasahara ◽  
Ryosuke Iwai ◽  
Takuya Takahashi
Keyword(s):  
Molecular Dynamics ◽  
Glutamic Acid ◽  
Molecular Dynamics Simulations ◽  
Helical Conformation ◽  
Short Peptides ◽  
Computational Studies ◽  
Middle Region ◽  
Helix Conformation ◽  
Α Helix ◽  
Dynamics Simulations

Elucidating the molecular mechanism of helix–coil transitions of short peptides is a long-standing conundrum in physical chemistry. Although the helix–coil transitions of poly-glutamic acid (PGA) have been extensively studied, the molecular details of its unfolding process still remain unclear. We performed all-atom canonical molecular dynamics simulations for a 20-residue PGA, over a total of 19 μs, in order to investigate its helix-unfolding processes in atomic resolution. Among the 28 simulations, starting with the α-helical conformation, all showed an unfolding process triggered by the unwinding of terminal residues, rather than by kinking and unwinding of the middle region of the chain. The helix–coil–helix conformation which is speculated by the previous experiments was not observed. Upon comparison between the N- and C-termini, the latter tended to be unstable and easily unfolded. While the probabilities of helix elongation were almost the same among the N-terminal, middle, and C-terminal regions of the chain, unwinding of the helix was enriched at the C-terminal region. The turn and 310-helix conformations were kinetic intermediates in the formation and deformation of α-helix, consistent with the previous computational studies for Ala-based peptides.

scholarly journals Molecular Basis for Spirocycle Formation in the Paraherquamide Biosynthetic Pathway

2019 ◽  
Author(s):  
Amy E. Fraley ◽  
Kersti Caddell Haatveit ◽  
Ying Ye ◽  
Samantha P. Kelly ◽  
Sean A. Newmister ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Natural Products ◽  
Molecular Dynamics Simulations ◽  
Molecular Basis ◽  
Biosynthetic Pathway ◽  
Three Dimensional ◽  
Enzymatic Reactions ◽  
Computational Studies ◽  
Penicillium Simplicissimum ◽  
Dynamics Simulations

<div> <div> <div> <p>The paraherquamides are potent anthelmintic natural products with complex heptacyclic scaffolds. One key feature of these molecules is the spiro-oxindole moiety that lends a strained three-dimensional architecture to these structures. The flavin monooxygenase PhqK was found to catalyze spirocycle formation through two parallel pathways in the biosynthesis of paraherquamides A and G. Two new paraherquamides (K and L) were isolated from a ΔphqK strain of Penicillium simplicissimum, and subsequent enzymatic reactions with these compounds generated two additional metabolites paraherquamides M and N. Crystal structures of PhqK in complex with various substrates provided a foundation for mechanistic analyses and computational studies. While it is evident that PhqK can react with various substrates, reaction kinetics and molecular dynamics simulations indicated that the dioxepin-containing paraherquamide L was the favored substrate. Through this effort, we have elucidated a key step in the biosynthesis of the paraherquamides, and provided a rationale for the selective spirocyclization of these powerful anthelmintic agents. </p></div></div><div><div> </div> </div> </div>

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