Evaluating the Performance of a Non-Bonded Cu2+ Model Including Jahn−Teller Effect into the Binding of Tyrosinase Inhibitors

Abstract

<jats:p>Tyrosinase (TYR) is a metalloenzyme classified as a type-3 copper protein, which is involved in the synthesis of melanin through a catalytic process beginning with the conversion of the amino acid l-Tyrosine (l-Tyr) to l-3,4-dihydroxyphenylalanine (l-DOPA). It plays an important role in the mechanism of melanogenesis in various organisms including mammals, plants, and fungi. Herein, we used a combination of computational molecular modeling techniques including molecular dynamic (MD) simulations and the linear interaction energy (LIE) model to evaluate the binding free energy of a set of analogs of kojic acid (KA) in complex with TYR. For the MD simulations, we used a dummy model including the description of the Jahn–Teller effect for Cu2+ ions in the active site of this enzyme. Our results show that the LIE model predicts the TYR binding affinities of the inhibitor in close agreement to experimental results. Overall, we demonstrate that the classical model provides a suitable description of the main interactions between analogs of KA and Cu2+ ions in the active site of TYR.</jats:p>

Refining details of the structural and electronic properties of the CuB site in pMMO enzyme through sequential molecular dynamics/CPKS-EPR calculations

“…The model has been validated adequately in studies investigating copper proteins' structural and dynamical properties. 22,36 These results have shown that this model reproduces the coordination properties of the copper ion in proteins active sites correctly, in line with some results obtained from quantum chemical methods, with the advantage of allowing a sizeable conformational sampling of the protein structure in the presence of the solvent. The protein was surrounded with water molecules using a cubic box of 100.89 Å of side with a minimum distance of 12 Å between any atom of the protein and the faces of the cube.…”

Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations

“…Initially, it should be highlighted that our molecular docking results using the Virtual Docker (MVD) package and MOLDOCK method [ 22 ] have been successfully applied for TYR systems [ 18 , 19 , 20 , 21 ]. In Figure 2 , the docked conformation of the weakest and strongest potent 1,2,3-triazole-based KA inhibitor ( 6h and 6o , respectively) show suitable conformations into the TYR catalytic site where the KA ring is close to the crystallographic structure of the KA complex.…”

“…This study shines a light on the TYR inhibition mechanism by providing structural and energetic information that agrees with experimental proposals. Moreover, all applied computational procedures here have been successfully validated by our research group [ 18 , 19 , 20 , 21 ].…”

The Physical Chemistry and Chemical Physics (PCCP) Section of the International Journal of Molecular Sciences in Its Publications: The First 300 Thematic Articles in the First 3 Years

“…This direction is represented by 39 articles [ 28 , 35 , 129 , 134 , 136 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 ]. Their distribution, according to the above types, is presented in Table 7 .…”

“…In this research, the given reaction between cyclopentadiene and methyl acrylate was computationally investigated in the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate, [BMIM] [PF 6 ], as a basis for the validation of the OPLS-VSIL to properly reproduce a reaction medium environment. The articles of group ( c ) include publications [ 28 , 129 , 136 , 193 , 195 , 199 , 200 , 202 , 208 , 209 , 212 , 213 , 215 , 220 ]: in most of them [ 129 , 136 , 195 , 199 , 200 , 202 , 208 , 209 , 212 , 215 ], the objects of quantum chemical calculations were the chelate and macrocyclic coordination compounds of various s -, p -, d -, and f -elements. The most significant of them seems to be publication [ 136 ], devoted to Pu(IV) and Pu(VI) complexes with tridentate (NNN)-donor-atomic ligands, in particular, di(pyridyl-2)amine, 1,3-diamino-2-azapropane, and 2,6-di(pyridyl-2) pyridine, the results of which can be very useful in the development of new extractants and organic sensors of plutonium.…”