scholarly journals Using molecular dynamics simulations to evaluate active designs of cephradine hydrolase by molecular mechanics/Poisson–Boltzmann surface area and molecular mechanics/generalized Born surface area methods

RSC Advances ◽  
2019 ◽  
Vol 9 (24) ◽  
pp. 13868-13877 ◽  
Author(s):  
Jing Xue ◽  
Xiaoqiang Huang ◽  
Yushan Zhu
Keyword(s):  
Molecular Dynamics ◽  
Molecular Mechanics ◽  
Surface Area ◽  
Assessment Method ◽  
Dynamics Simulation ◽  
Enzyme Design ◽  
Generalized Born ◽  
Computational Enzyme Design ◽  
Poisson Boltzmann ◽  
Dynamics Simulations

A quantitative assessment method for computational enzyme design was developed to rank the active designs of cephradine hydrolase based on molecular dynamics simulation.

scholarly journals In silico discovery of SARS-CoV-2 main protease inhibitors from the carboline and quinoline database

2021 ◽  
Author(s):  
Eldar Muhtar ◽  
Mengyang Wang ◽  
Haimei Zhu
Keyword(s):  
Molecular Dynamics ◽  
Molecular Mechanics ◽  
Protease Inhibitors ◽  
Surface Area ◽  
In Silico ◽  
Binding Energies ◽  
Main Protease ◽  
Poisson Boltzmann ◽  
Dynamics Simulations ◽  
Potential Inhibitors

Aim: SARS-CoV-2 caused more than 3.8 million deaths according to the WHO. In this urgent circumstance, we aimed at screening out potential inhibitors targeting the main protease of SARS-CoV-2. Materials & methods: An in-house carboline and quinoline database including carboline, quinoline and their derivatives was established. A virtual screening in carboline and quinoline database, 50 ns molecular dynamics simulations and molecular mechanics Poisson−Boltzmann surface area calculations were carried out. Results: The top 12 molecules were screened out preliminarily. The molecular mechanics Poisson−Boltzmann surface area ranking showed that p59_7m, p12_7e, p59_7k stood out with the lowest binding energies of -24.20, -17.98, -17.67 kcal/mol, respectively. Conclusion: The study provides powerful in silico results that indicate the selected molecules are valuable for further evaluation as SARS-CoV-2 main protease inhibitors.

scholarly journals Molecular Docking and Dynamics Investigations for Identifying Potential Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2: Repurposing of Approved Pyrimidonic Pharmaceuticals for COVID-19 Treatment

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7458
Author(s):  
Amin Osman Elzupir
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Mechanics ◽  
Surface Area ◽  
Active Sites ◽  
Inhibitory Effect ◽  
Binding Energies ◽  
Poisson Boltzmann ◽  
The Stability ◽  
Dynamics Simulations

This study demonstrates the inhibitory effect of 42 pyrimidonic pharmaceuticals (PPs) on the 3-chymotrypsin-like protease of SARS-CoV-2 (3CLpro) through molecular docking, molecular dynamics simulations, and free binding energies by means of molecular mechanics–Poisson Boltzmann surface area (MM-PBSA) and molecular mechanics–generalized Born surface area (MM-GBSA). Of these tested PPs, 11 drugs approved by the US Food and Drug Administration showed an excellent binding affinity to the catalytic residues of 3CLpro of His41 and Cys145: uracil mustard, cytarabine, floxuridine, trifluridine, stavudine, lamivudine, zalcitabine, telbivudine, tipiracil, citicoline, and uridine triacetate. Their percentage of residues involved in binding at the active sites ranged from 56 to 100, and their binding affinities were in the range from −4.6 ± 0.14 to −7.0 ± 0.19 kcal/mol. The molecular dynamics as determined by a 200 ns simulation run of solvated docked complexes confirmed the stability of PP conformations that bound to the catalytic dyad and the active sites of 3CLpro. The free energy of binding also demonstrates the stability of the PP–3CLpro complexes. Citicoline and uridine triacetate showed free binding energies of −25.53 and −7.07 kcal/mol, respectively. Therefore, I recommend that they be repurposed for the fight against COVID-19, following proper experimental and clinical validation.

A Molecular Dynamics Study on Effects of Nanostructural Clearances on Thermal Resistance at an Interface Between Liquid and Solid

2008 ◽  
Author(s):  
Masahiko Shibahara ◽  
Kiyoshi Takeuchi
Keyword(s):  
Molecular Dynamics ◽  
Thermal Resistance ◽  
Surface Area ◽  
Resistance Index ◽  
Dynamics Simulation ◽  
Fluid Density ◽  
Resistance Change ◽  
Molecular Scale ◽  
Dynamics Simulations ◽  
Solid Walls

The classical molecular dynamics simulation was conducted in order to clarify the effects of the surface structural clearances in nanometer scale on thermal resistance at a liquid-solid interface as well as static and dynamic behaviours of fluid molecules in the vicinity of the surface. A liquid molecular region confined between the solid walls, of which the interparticle potential was Lennard-Jones type, was employed as a calculation system. The thermal resistance between the liquid molecular region and the solid walls with nanostructures was calculated by the heat flux and the temperature jump obtained in the molecular dynamics simulations. With changing the surface structural clearances from 0 to 2.81 nm the thermal resistance between the liquid molecular region and the solid walls with nanostructures once decreased and became the minimum value when the structural clearances were about 0.7 nm. Surface area in molecular scale and fluid density at the interface were dependent on the surface structural clearances and the thermal resistance index calculated by the relative surface area in molecular scale and the relative fluid density at the interface could predict thermal resistance change depending on the nanostructural clearances. Surface nanostructural clearances affected the fluid molecular motions along the heat transfer direction only when the molecular velocity was averaged over a specific characteristic time. Surface nanostructural clearances affected the diffusion behaviours of fluid molecules in the vicinity of the surface too.

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