scholarly journals Accelerated Molecular Dynamics Applied to the Peptaibol Folding Problem

2019 ◽  
Vol 20 (17) ◽  
pp. 4268
Author(s):  
Chetna Tyagi ◽  
Tamás Marik ◽  
Csaba Vágvölgyi ◽  
László Kredics ◽  
Ferenc Ötvös
Keyword(s):  
Molecular Dynamics ◽  
Enhanced Sampling ◽  
New Approach ◽  
E Coli ◽  
Accelerated Molecular Dynamics ◽  
Simulation Techniques ◽  
Unfolded State ◽  
Folding Dynamics ◽  
Transmembrane Channels ◽  
Dynamics Simulations

The use of enhanced sampling molecular dynamics simulations to facilitate the folding of proteins is a relatively new approach which has quickly gained momentum in recent years. Accelerated molecular dynamics (aMD) can elucidate the dynamic path from the unfolded state to the near-native state, “flattened” by introducing a non-negative boost to the potential. Alamethicin F30/3 (Alm F30/3), chosen in this study, belongs to the class of peptaibols that are 7–20 residue long, non-ribosomally synthesized, amphipathic molecules that show interesting membrane perturbing activity. The recent studies undertaken on the Alm molecules and their transmembrane channels have been reviewed. Three consecutive simulations of ~900 ns each were carried out where N-terminal folding could be observed within the first 100 ns, while C-terminal folding could only be achieved almost after 800 ns. It took ~1 μs to attain the near-native conformation with stronger potential boost which may take several μs worth of classical MD to produce the same results. The Alm F30/3 hexamer channel was also simulated in an E. coli mimicking membrane under an external electric field that correlates with previous experiments. It can be concluded that aMD simulation techniques are suited to elucidate peptaibol structures and to understand their folding dynamics.

scholarly journals Conformational Changes of Glutamine 5′-Phosphoribosylpyrophosphate Amidotransferase for Two Substrates Analogue Binding: Insight from Conventional Molecular Dynamics and Accelerated Molecular Dynamics Simulations

2021 ◽  
Vol 9 ◽  
Author(s):  
Congcong Li ◽  
Siao Chen ◽  
Tianci Huang ◽  
Fangning Zhang ◽  
Jiawei Yuan ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Conformational Changes ◽  
Active Sites ◽  
Salt Bridge ◽  
Enhanced Sampling ◽  
Ongoing Research ◽  
Accelerated Molecular Dynamics ◽  
Flexible Loop ◽  
Dynamics Simulations ◽  
Phosphoribosylpyrophosphate Amidotransferase

Glutamine 5′-phosphoribosylpyrophosphate amidotransferase (GPATase) catalyzes the synthesis of phosphoribosylamine, pyrophosphate, and glutamate from phosphoribosylpyrophosphate, as well as glutamine at two sites (i.e., glutaminase and phosphoribosylpyrophosphate sites), through a 20 Å NH3 channel. In this study, conventional molecular dynamics (cMD) simulations and enhanced sampling accelerated molecular dynamics (aMD) simulations were integrated to characterize the mechanism for coordination catalysis at two separate active sites in the enzyme. Results of cMD simulations illustrated the mechanism by which two substrate analogues, namely, DON and cPRPP, affect the structural stability of GPATase from the perspective of dynamic behavior. aMD simulations obtained several key findings. First, a comparison of protein conformational changes in the complexes of GPATase–DON and GPATase–DON–cPRPP showed that binding cPRPP to the PRTase flexible loop (K326 to L350) substantially effected the formation of the R73-DON salt bridge. Moreover, only the PRTase flexible loop in the GPATase–DON–cPRPP complex could remain closed and had sufficient space for cPRPP binding, indicating that binding of DON to the glutamine loop had an impact on the PRTase flexible loop. Finally, both DON and cPRPP tightly bonded to the two domains, thereby inducing the glutamine loop and the PRTase flexible loop to move close to each other. This movement facilitated the transfer of NH3 via the NH3 channel. These theoretical results are useful to the ongoing research on efficient inhibitors related to GPATase.

scholarly journals Molecular Dynamics Simulations of the Predicted E. Coli FtsB-FtsL Tetrameric Complex

2017 ◽  
Vol 112 (3) ◽  
pp. 501a
Author(s):  
Gladys Diaz Vazquez ◽  
Samson Condon ◽  
Qiang Cui ◽  
Alessandro Senes
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
E Coli ◽  
Dynamics Simulations ◽  
Tetrameric Complex

SPONGE : A GPU‐Accelerated Molecular Dynamics Package with Enhanced Sampling and AI‐Driven Algorithms

2021 ◽  
Author(s):  
Yu‐Peng Huang ◽  
Yijie Xia ◽  
Lijiang Yang ◽  
Jiachen Wei ◽  
Yi Isaac Yang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Enhanced Sampling ◽  
Accelerated Molecular Dynamics

scholarly journals The role of side chains in the interaction of new antitumor pyrimidoacridinetriones with DNA: molecular dynamics simulations.

2000 ◽  
Vol 47 (1) ◽  
pp. 47-57 ◽  
Author(s):  
J Mazerski ◽  
I Antonini ◽  
S Martelli
Keyword(s):  
Molecular Dynamics ◽  
Rational Design ◽  
Md Simulations ◽  
Ring System ◽  
Side Chain ◽  
Side Chains ◽  
Intercalation Complex ◽  
Highly Active ◽  
Simulation Techniques ◽  
Dynamics Simulations

Pyrimidoacridinetriones (PATs) are a new group of highly active antitumor compounds. It seems reasonable to assume that, like for some other acridine derivatives, intercalation into DNA is a necessary, however not a sufficient condition for antitumor activity of these compounds. Rational design of new compounds of this chemotype requires knowledge about the structure of the intercalation complex, as well as about interactions responsible for its stability. Computer simulation techniques such as molecular dynamics (MD) may provide valuable information about these problems. The results of MD simulations performed for three rationally selected PATs are presented in this paper. The compounds differ in the number and position of side chains. Each of the compounds was simulated in two systems: i) in water, and ii) in the intercalation complex with the dodecamer duplex d(GCGCGCGCGCGC)2. The orientation of the side chain in relation to the ring system is determined by the position of its attachment. Orientation of the ring system inside the intercalation cavity depends on the number and position of side chain(s). The conformations of the side chain(s) of all PATs studied in the intercalation complex were found to be very similar to those observed in water.

scholarly journals An Efficient GaMD Multi-Level Enhanced Sampling Strategy: Application to Polarizable Force Fields Simulations of Large Biological Systems

2021 ◽  
Author(s):  
Fréderic Célerse ◽  
Theo Jaffrelot-Inizan ◽  
Louis Lagardère ◽  
Olivier Adjoua ◽  
Pierre Monmarché ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Adaptive Sampling ◽  
Sampling Strategy ◽  
Umbrella Sampling ◽  
Potential Of Mean Force ◽  
Enhanced Sampling ◽  
Polarizable Force Field ◽  
Accelerated Molecular Dynamics ◽  
Polarizable Force Fields ◽  
Multi Level

We detail a novel multi-level enhanced sampling strategy grounded on Gaussian accelerated Molecular Dynamics (GaMD). First, we propose a GaMD multi-GPUs-accelerated implementation within the Tinker-HP molecular dynamics package. We then introduce the new "dual-water" mode and its use with the flexible AMOEBA polarizable force field. By adding harmonic boosts to the water stretching and bonding terms, it accelerates the solvent-solute interactions while enabling speedups thanks to the use of fast multiple--timestep integrators. To further reduce time-to-solution, we couple GaMD to Umbrella Sampling (US). The GaMD—US/dual-water approach is tested on the 1D Potential of Mean Force (PMF) of the CD2-CD58 system (168000 atoms) allowing the AMOEBA PMF to converge within 1 kcal/mol of the experimental value. Finally, Adaptive Sampling (AS) is added enabling AS-GaMD capabilities but also the introduction of the new Adaptive Sampling--US--GaMD (ASUS--GaMD) scheme. The highly parallel ASUS--GaMD setup decreases time to convergence by respectively 10 and 20 compared to GaMD--US and US.

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