TY - JOUR
T1 - Prediction of the interaction of metallic moieties with proteins: An update for protein-ligand docking techniques
AU - Sciortino, Giuseppe
AU - Rodríguez-Guerra Pedregal, Jaime
AU - Lledós, Agustí
AU - Garribba, Eugenio
AU - Maréchal, Jean Didier
PY - 2018/1/5
Y1 - 2018/1/5
N2 - © 2017 Wiley Periodicals, Inc. 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. © 2017 Wiley Periodicals, Inc.
AB - © 2017 Wiley Periodicals, Inc. 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. © 2017 Wiley Periodicals, Inc.
KW - coordination chemistry and metal complexes
KW - protein binding site prediction
KW - protein-ligand docking
U2 - 10.1002/jcc.25080
DO - 10.1002/jcc.25080
M3 - Article
C2 - 29076256
VL - 39
SP - 42
EP - 51
JO - Journal of Computational Chemistry
JF - Journal of Computational Chemistry
SN - 0192-8651
IS - 1
ER -