Prediction of the interaction of metallic moieties with proteins: An update for protein‐ligand docking techniques

Abstract

In this article, we present a new approach to expand the range of application of protein-ligand docking methods in the prediction of the interaction of coordination complexes (i.e., metallodrugs, natural and artificial cofactors, etc.) with proteins. To do so, we assume that, from a pure computational point of view, hydrogen bond functions could be an adequate model for the coordination bonds as both share directionality and polarity aspects. In this model, docking of metalloligands can be performed without using any geometrical constraints or energy restraints. The hard work consists in generating the convenient atom types and scoring functions. To test this approach, we applied our model to 39 high-quality X-ray structures with transition and main group metal complexes bound via a unique coordination bond to a protein. This concept was implemented in the protein-ligand docking program GOLD. The results are in very good agreement with the experimental structures: the percentage for which the RMSD of the simulated pose is smaller than the X-ray spectra resolution is 92.3% and the mean value of RMSD is < 1.0 Å . Such results also show the viability of the method to predict metal complexes-proteins interactions when the X-ray structure is not available. This work could be the first step for novel applicability of docking techniques in medicinal and bioinorganic chemistry and appears generalizable enough to be implemented in most protein-ligand docking programs nowadays available.

Modeling zinc‐oxygen coordination in histone deacetylase: A comparison of semiempirical methods performance

“…A simple comparison between the mean RMSD values shown in Figure or between the RMSD values presented for each complex in Table with the X‐ray resolution values of the crystals does not allow to identify a clear fault for any method, since the RMSD values are lower than the resolution of the crystals . However, when analyzing each case, it is possible to perceive some significant differences, as can be observed for (4) (PDB: 5G0H) when optimized by the PM7 method, in which the ligand goes from a bidentate coordination interaction to a monodentate one, distancing the hydroxyl oxygen of the hydroxamic acid group away from the Zn(II) ion (Figure ).…”

Unveiling the binding interaction of zinc (II) complexes of homologous Schiff‐base ligands on the surface of BSA protein: A combined experimental and theoretical approach

“…It is well known that metal complexes undergo coordination/dipole–dipole/hydrogen bonding interaction with polar/charged amino acid residues such as aspartic acid, asparagine, lysine, histidine etc. of protein molecule . These amino acid residues are mostly present in the outer surface of protein molecule and exposed to aqueous environment, therefore, the metal ion centre can easily coordinatively interact with these residues without entering into the hydrophobic pocket of protein molecules.…”

Biospeciation of Potential Vanadium Drugs of Acetylacetonate in the Presence of Proteins

“…2 , activating one, two or three equatorial coordination positions, respectively, with dummy hydrogen atoms (Sciortino et al, 2017(Sciortino et al, , 2018a(Sciortino et al, ,b, 2019a. All the possible moieties…”