scholarly journals Computational method for relative binding energies of enzyme-substrate complexes

1996 ◽  
Vol 5 (2) ◽  
pp. 348-356 ◽  
Author(s):  
Tao Zhang ◽  
Daniel E. Koshland
Keyword(s):  
Binding Energies ◽  
Computational Method ◽  
Enzyme Substrate ◽  
Relative Binding

scholarly journals Simultaneous molecular docking of different ligands to His6-tagged organophosphorus hydrolase as an effective tool for assessing their effect on the enzyme

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7684 ◽  
Author(s):  
Aysel Aslanli ◽  
Elena Efremenko
Keyword(s):  
Antibiotic Resistance ◽  
Molecular Docking ◽  
Active Sites ◽  
Homoserine Lactone ◽  
Hydrolytic Activity ◽  
Binding Energies ◽  
Organophosphorus Hydrolase ◽  
Combined Application ◽  
Enzyme Substrate ◽  
Long Chain

Background Enzymatic hydrolysis of N-acyl homoserine lactones (AHLs), which are signaling molecules responsible for the development of antibiotic resistance in gram-negative bacteria, is a potential solution to overcoming antibiotic resistance problem. It has been established that hexahistidine-tagged organophosphorus hydrolase (His6-OPH) exhibits lactonase activity against a number of AHLs and that the combined application of His6-OPH with β-lactam antibiotics leads to an increase in the efficiency of the action of both the enzyme and antibiotics. The use of computational methods can be an effective way to search for and select from the known antibiotics to find the most rational “partners” for combining with this enzyme and creating effective antibacterial agents with a dual (lactonase and antibacterial) functional activity. Methods In this study, by using AutoDock Vina and Gromacs softwares the molecular docking and the molecular dynamics methods were adopted to simulate models of puromycin, ceftiofur, and/or AHLs docked to the surface of a dimer molecule of His6-OPH and to study their binding properties. GABEDIT and GAMESS-US packages were used to generate and simulate electron densities of docked AHLs. Results Interactions of N-butyryl-DL-homoserine lactone (C4-HSL), N-(3-oxooctanoyl)-L-homoserine lactone (C8-HSL) and N-(3-oxododecanoyl)-L-homoserine lactone (C12-HSL) with His6-OPH dimer active sites in the presence of puromycin and ceftiofur were simulated and studied. The possible intersection of long-chain AHLs with antibiotic molecules in the active sites of the enzyme was revealed. The binding energies of antibiotics and AHLs with the His6-OPH surface were estimated. Statistically significant differences (p = 0.003) were observed between the values calculated for both C4-HSL and C12-HSL, whereas there were no statistically significant differences between the values of the other groups (p ≥ 0.100). The binding energies of AHLs with His6-OPH were slightly higher as compared with the binding energies of antibiotics with the enzyme. The dynamics of the most probable models obtained from docking were investigated. RMSD and RMSF analysis of His6-OPH-AHL complexes in the absence and presence of antibiotics were performed. The interaction energy values of antibiotics and AHLs with the His6-OPH were assessed. Significant increase of the AHLs steadiness in enzyme-substrate complexes in the presence of antibiotics was revealed. The interaction between His6-OPH and C12-HSL was established as thermodynamically more favored. Conclusions It has been established that the studied antibiotics puromycin and ceftiofur steady the enzyme-substrate complexes, but at the same time lead to a decrease in the long-chain AHL-hydrolytic activity of His6-OPH in such a combination as compared to a native enzyme, and, therefore, it should be taken into account when creating a therapeutic composition based on combining antibiotics with His6-OPH.

scholarly journals Non-equilibrium Binding Energy Determined Using Alpha-amylase Catalysed Amylolysis of Gelatinised Starch as a Probable Generalisable Model and Importance

2020 ◽  
pp. 9-23
Author(s):  
Ikechukwu I. Udema
Keyword(s):  
Binding Energy ◽  
Thermal Energy ◽  
Enzyme Assay ◽  
Substrate Inhibition ◽  
Binding Energies ◽  
Binding Interaction ◽  
Enzyme Substrate ◽  
Equilibrium Binding ◽  
Non Equilibrium

Objectives: This research was undertaken to determine the non–equilibrium binding energy by calculation after substituting experimental data into derived equations, present its role distinct from energy associated with activated enzyme–substrate (ES) complex and ultimately elucidate the importance of binding energies. Background: There are overwhelming pieces of evidence in the literature that binding interaction is essential for the ultimate transformation of a substrate, inhibition of vital enzymes of pathogens, covid-19 in particular. Intrinsic binding energy herein referred to as non–equilibrium binding energy and energy associated with activated ES are seen to be chemical in origin. Much attention seemed not to be given to theoretical approach to the determination of non–equilibrium binding energy. Methods: Experimental approach (Bernfeld method of enzyme assay) and calculational. Results and Discussion: The non–equilibrium translational (2.691–2.726 kJ/mol) and total electrostatic energies (2.755-3.154 kJ/mol) were > than the thermal energy at 310.15 k. The interfacial distance between the bullet and target molecule was expectedly very short; the range was between 6.672 and 7.570 exp (- 12) m. This was attributed to the interaction between charged enzyme and weakly polar substrate. Conclusion: The equations of non–equilibrium and translational energies were derivable. The binding interaction serves to fix the bullet molecule on or into the target (supra) molecule before the commencement of transition state formation. The non–equilibrium binding interactions of the bullet (drugs, substrate, etc) and target (receptors e.g. enzymes, pathogens such as Covid–19, Plasmodium etc) and the ultimate complex are likely to be stabilised against the thermal energy in furtherance of enzymatic and drug action since the electrostatic interaction energy is higher than thermal energy.

A comparison of the relative binding energies of H+ and NO+ to aromatic and haloaromatic bases by high pressure mass spectrometry

1982 ◽  
Vol 60 (7) ◽  
pp. 910-915 ◽  
Author(s):  
John A. Stone ◽  
Dena E. Splinter ◽  
Soon Yau Kong
Keyword(s):  
Mass Spectrometry ◽  
High Pressure ◽  
Proton Affinity ◽  
Marked Effect ◽  
Ion Source ◽  
Binding Energies ◽  
Absolute Value ◽  
Pulsed Electron Beam ◽  
Relative Binding ◽  
Benzene Toluene

Proton transfer equilibria [Formula: see text] and NO+ transfer equilibria [Formula: see text] have been studied for the following bases B, benzene, toluene, o-, m-, and p-xylene. NO+ transfer equilibria for fluoro- and chlorobenzene have also been studied. Pulsed electron beam, high-pressure ion source mass spectrometry has been used to obtain the equilibrium constant K and hence the free energy changes ΔG0 and from van't Hoff plots, ΔH0 and ΔS0. Entropy changes are in general much smaller for NO+ transfer than for H+ transfer but the magnitude of the changes in the proton affinity and NO+ affinity of toluene caused by a fluorine substituent is about the same, even though the absolute value of the proton affinity is greater by a factor of 4. The position of the F substituent on toluene has a marked effect on proton affinity but no effect on NO+ affinity. The latter appears to be responsive only to the inductive effect.

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