Enzyme inhibitors binding

Not all enzyme inhibitors bind through reversible interactions. In some cases enzymes are inactivated by formation of covalent complexes with inhibitory molecules. 

The "suicide inhibitor." This enzyme inhibitor binds irreversibly to the enzyme protein, permanently inhibiting the enzyme. 

Fig. 1 Equilibrium between reactants (E + I) and noncovalent complex (E- I ) in a typical enzyme-inhibitor binding process...

Based Free Energy Parameterization of Enzyme-Inhibitor Binding. Application to FDV-1-Protease Inhibitor Design. 

Wallqvist, A., Jernigan, R. L. Covell, D. G. (1995). A preference-based free-energy parameterization of enzyme-inhibitor binding. Applications to HIV-l-protease inhibitor design. Protein Science 4, 1881-1903. 

FEP has been successfully used to calculate stability of mutant pro-teins, to examine solvation properties,and to predict relative free energies of enzyme—inhibitor binding in the human immunodeficiency virus 1 (HIV-1) protease system,... 

Figure 2 Two thermodynamic models that link perturbations in enzyme-inhibitor binding equilibria to values for interaction energies. E, enzyme I, inhibitor E l, enzyme-inhibitor complex AAGinteract energetic contribution of the perturbed interaction to complex formation AGso1v,e energy of desolvation for the enzyme AGsoiv, energy of desolvation for the inhibitor AGresoiv, energy of resolvation of the E l complex.

Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulation. 

A. Wallqvist, R. L. Jernigan, and D. G. Covell, Protein Sei., 4, 1881 (1995). A Preference-Based Free-Energy Parameterization of Enzyme Inhibitor Binding. Applications to HIV-1 Protease Inhibitor Design. 

Arsenate, a phosphate analog and enzyme inhibitor, binds between Ser-102 and Zn sites A and B. The guanidinium group of Arg-166 is within a H-bonding distance from the arsenate site. In the absence of any particular acid or base of the protein to facilitate the proton transfer, metals are apparently able to activate... 

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