scholarly journals Net charge changes in the calculation of relative ligand-binding free energies via classical atomistic molecular dynamics simulation

2013 ◽  
Vol 35 (3) ◽  
pp. 227-243 ◽  
Author(s):  
Maria M. Reif ◽  
Chris Oostenbrink
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Ligand Binding ◽  
Dynamics Simulation ◽  
Free Energies ◽  
Net Charge ◽  
Binding Free Energies

Zn2+ion of the snake venom metalloproteinase (SVMP) plays a critical role in ligand binding: a molecular dynamics simulation study

RSC Advances ◽  
2015 ◽  
Vol 5 (86) ◽  
pp. 70566-70576 ◽  
Author(s):  
Sathishkumar Chinnasamy ◽  
Selvaraman Nagamani ◽  
Karthikeyan Muthusamy
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Ligand Binding ◽  
Blood Coagulation ◽  
Snake Venom ◽  
Simulation Study ◽  
Tissue Damage ◽  
Critical Role ◽  
Dynamics Simulation ◽  
Snake Venom Metalloproteinase

Snake venom metalloproteinase (SVMP) is one of the major components of snake venom and it is a root causative agent for edema, local tissue damage, inflammation, blood coagulation and hemorrhage during the snake bite.

Investigations on the mechanisms of interactions between matrix metalloproteinase 9 and its flavonoid inhibitors using a combination of molecular docking, hybrid quantum mechanical/molecular mechanical calculations, and molecular dynamics simulations

2014 ◽  
Vol 92 (9) ◽  
pp. 821-830 ◽  
Author(s):  
Zhi-Guang Zhou ◽  
Qi-Zheng Yao ◽  
Dong Lei ◽  
Qing-Qing Zhang ◽  
Ji Zhang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Biological Activities ◽  
Dynamics Simulation ◽  
Quantum Mechanical ◽  
Free Energies ◽  
Hydrogen Bond Networks ◽  
Dynamics Simulations ◽  
Binding Free Energies

Many experimental studies have found that flavonoids can inhibit the activities of matrix metalloproteinases (MMPs), but the relevant mechanisms are still unclear. In this paper, the interaction mechanisms of MMP-9 with its five flavonoid inhibitors are investigated using a combination of molecular docking, hybrid quantum mechanical and molecular mechanical (QM/MM) calculations, and molecular dynamics simulations. The molecular dynamics simulation results show a good linear correlation between the calculated binding free energies of QM/MM−Poisson–Boltzmann surface area (PBSA) and the experimental −log(EC50) regarding the studied five flavonoids on MMP-9 inhibition in explicit solvent. It is found that compared with the MM−PBSA method, the QM/MM−PBSA method can obviously improve the accuracy for the calculated binding free energies. The predicted binding modes of the five flavonoid−MMP-9 complexes reveal that the different hydrogen bond networks can form besides producing the Zn−O coordination bonds, which can reasonably explain previous experimental results. The agreement between our calculated results and the previous experimental facts indicates that the force field parameters used here are effective and reliable for investigating the systems of flavonoid−MMP-9 interactions, and thus, these simulations and analyses could be reproduced for the other related systems involving protein−ligand interactions. This paper may be helpful for designing the new MMP-9 inhibitors having higher biological activities by carrying out the structural modifications of flavonoid molecules.

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