Introduction of the Topic: Metalloenzymes are a superfamily of enzymes that possess metal ions as a cofactor and catalyze a plethora of reactions such as oxidations, reductions, biosynthesis, and drug metabolism. These reactions are regulated by synchronized choreography of some strategic protein residues that act as a signal to communicate with the metal center to perform a specific function for the catalysis. Such choreography of the protein's residues is, nowadays, routinely studied by Molecular Dynamics (MD) Simulations. This special issue covers two important aspects of simulations of metalloenzymes: 1) accurate and efficient modeling of metal ions during simulations and 2) a few applications of molecular dynamics simulations to study the conformational changes en route to catalysis by metalloenzymes/metalloproteins. These articles are written by some leading researchers in this field. Here, we briefly introduce some of these articles in this new collection.
A new algorithm for fast and accurate potentials for Zinc containing proteins: The development of a potential energy function that provides accuracy at QM standard and efficiency at MM scale is a long-time goal for computational chemists. In this special issue, Zhang and coworkers have developed an algorithm based on an enhanced selforganizing incremental high dimensional neural network-deep potential model for zinccontaining metalloproteins (https://doi.org/10.3389/fchem.2021.692200). The authors have shown that calculated atomic forces, potential energy, and atomic charges are in good agreement with quantum mechanical calculations. Therefore, the proposed model of the Zhang group could have a significant impact on the simulations of the metalloenzymes since it incorporates the polarization effect in the simulation with the speed at the MM level.A new fluctuating 12-6-4 Ion Model for Metal Ions: An accurate modeling of metal ions is crucial during MD simulations. The previously proposed 12-6 Lennard-Jones nonbonded ion model by the Merz group was efficient but couldn't produce the experimental hydration-free energy which was further corrected by the 12-6-4 model by the same group. However, it was found that the upgraded 12-6-4 model overestimates the coordination number of highly charged metal ions. In the current issue, Pengfei Li proposed a fluctuating charge 12-6-4 model which further rectifies such overestimations of coordination numbers (https://doi.org/10.3389/fchem.2021.721960). In fact, the author shows that the MD simulations using fluctuating charge 12-6-4 model successfully reproduced the results of the previous ab-initio MD simulations.
