myPresto/omegagene: a GPU-accelerated molecular dynamics simulator tailored for enhanced conformational sampling methods with a non-Ewald electrostatic scheme

Kasahara, Kota; Ma, Benson; Goto, Kota; DasGupta, Bhaskar; Higo, Junichi; Fukuda, Ikuo; Mäshimo, T.; Akiyama, Yutaka; Nakamura, Haruki

doi:10.2142/biophysico.13.0_209

Cited by 38 publications

(35 citation statements)

References 42 publications

(46 reference statements)

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“…We also used myPresto ligand docking utilities to dock the selected drugs to the protease under default settings. myPresto is tailored for a single process execution with a single GPU (Graphics Processing Unit), in order to optimize the enhanced conformational sampling methods (Kasahara et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

Theoretical Molecular Docking Study of the Structural Disruption of the Viral 3CL-Protease of COVID19 Induced by Binding of Capsaicin, Piperine and Curcumin Part 1: A Comparative Study with Chloroquine and Hydrochloroquine Two Antimalaric Drugs

González

Lossada

Moncayo

et al. 2020

Preprint

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The global pandemic caused by infections of the new coronavirus (COVID-19) makes it necessary to find possible less toxic and easily accessible therapeutic agents. In this study, we used strategies docking and molecular dynamics to analyze phytochemical compounds against FDA-approved antimalarial drugs recommended for the treatment of COVID-19. The evaluation was performed with the docking scores MolDock Score and Rerank Score calculated by Molegro Molecular. The DockThor server was used to generate the complexes and myPresto for the dynamic studies. Preliminary results suggested that piperine, capsaicin, and curcumin have the best docking scores and that they are capable of promoting structural changes in the viral protease by inducing folding of the enzyme. Curcumin and capsaicin bring the enzyme to a more compact conformational state compared to the native state, compared to chloroquine. Even though, it is unknown if these induced changes in protease are related to any inhibitory effect observed both in vitro and in vivo for any of these compounds. Further studies on the mechanisms of action of these compounds of interest are required, as well as experimental demonstrations. However, these results are interesting because they can serve as a starting point for subsequent experimental or/and in silico studies based on chemical structure-activity relationships taking these small molecules and their possible derivatives.

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Section: Methodsmentioning

confidence: 99%

Theoretical Molecular Docking Study of the Structural Disruption of the Viral 3CL-Protease of COVID19 Induced by Binding of Capsaicin, Piperine and Curcumin Part 1: A Comparative Study with Chloroquine and Hydrochloroquine Two Antimalaric Drugs

González

Lossada

Moncayo

et al. 2020

Preprint

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“…For each model, the following steps were performed using our MD simulation program, which is called myPresto/omegagene and is tailored for GE simulations (Kasahara et al, 2016). The protein conformation was randomized with a constanttemperature simulation at 800 K. By using 30 snapshots taken from a trajectory with an interval of 300 ps, 30 independent runs were simulated with a gradual decrease in the temperature from 629 to 296 K to estimate the density of states.…”

Section: Simulation Protocolmentioning

confidence: 99%

Effects of number of parallel runs and frequency of bias-strength replacement in generalized ensemble molecular dynamics simulations

Shimato

Kasahara

Higo

et al. 2019

PeerJ Physical Chemistry

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Background The generalized ensemble approach with the molecular dynamics (MD) method has been widely utilized. This approach usually has two features. (i) A bias potential, whose strength is replaced during a simulation, is applied. (ii) Sampling can be performed by many parallel runs of simulations. Although the frequency of the bias-strength replacement and the number of parallel runs can be adjusted, the effects of these settings on the resultant ensemble remain unclear. Method In this study, we performed multicanonical MD simulations for a foldable mini-protein (Trp-cage) and two unstructured peptides (8- and 20-residue poly-glutamic acids) with various settings. Results As a result, running many short simulations yielded robust results for the Trp-cage model. Regarding the frequency of the bias-potential replacement, although using a high frequency enhanced the traversals in the potential energy space, it did not promote conformational changes in all the systems.

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“…The most favored position was analyzed with MMV_2019_7.0.0, calculating the MolDock and Rerank functions (Thomsen and Christensen, 2006). We also used myPresto docking to couple selected drugs to protease in the default configuration (Kasahara et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

Molecular Docking and Molecular Dynamic Study of Two Viral Proteins Associated with SARS-CoV-2 with Ivermectin

Paz¹,

Lossada²,

Moncayo³

et al. 2020

Preprint

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The global pandemic caused by the new SARS-COV-2 coronavirus makes it necessary to search for drugs for its control. Within of this research it has been known that the ivermectin drug, a FDA-approved drugs which is formulated as an 80:20 mixture of ivermectin B1a and B1b and used commonly for parasitic infections, has an inhibitory effect on viruses, includes SARS-COV-2 at in vitro level. In the particular case of SARS-COV-2 its mechanism of action remains elusive and controversial. Interestingly, the energy of interaction of ivermectin with any of the proteins the SARS-CoV-2 and the possible structural alterations at the protein level that this drug can cause have not been reported. In this sense, we carried out a bioinformatics study with docking strategies and molecular dynamics to predict the binding and disturbance induced by ivermectin in proteins associated with SARS-CoV-2. We use DockThor and Molegro docking scores. The DockThor server and myPresto software were used to build complexes and dynamics studies, respectively. The results obtained suggested that ivermectin is capable of docking with the 3CL protease and the HR2 domain, and may promote structural changes in these proteins by inducing unfolding/folding. Specifically, ivermectin brings protease to a significantly more deployed conformational state and the HR2 domain to a more compact state compared to the native state. Finally, it is shown that B1a and B1b macrocyclic lactones have a behavior different from to each target protein. These results suggest a possible inhibitory effect against SARS-CoV-2 due to a synergistic role of this drug to spontaneously bind to two important proteins involve in the proliferation of this virus. However, more studies are required on this possible mechanism of action.

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myPresto/omegagene: a GPU-accelerated molecular dynamics simulator tailored for enhanced conformational sampling methods with a non-Ewald electrostatic scheme

Cited by 38 publications

References 42 publications

Theoretical Molecular Docking Study of the Structural Disruption of the Viral 3CL-Protease of COVID19 Induced by Binding of Capsaicin, Piperine and Curcumin Part 1: A Comparative Study with Chloroquine and Hydrochloroquine Two Antimalaric Drugs

Theoretical Molecular Docking Study of the Structural Disruption of the Viral 3CL-Protease of COVID19 Induced by Binding of Capsaicin, Piperine and Curcumin Part 1: A Comparative Study with Chloroquine and Hydrochloroquine Two Antimalaric Drugs

Effects of number of parallel runs and frequency of bias-strength replacement in generalized ensemble molecular dynamics simulations

Molecular Docking and Molecular Dynamic Study of Two Viral Proteins Associated with SARS-CoV-2 with Ivermectin

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