Natural deep eutectic solvents (NADES) represent a green alternative to common organic solvents in the biochemical industry due to their benign behavior and tailorable properties, in particular as media for enzymatic reactions. However, to fully exploit their potential in enzymatic reactions, there is a need for a more fundamental understanding of how these neoteric solvents influence the course of these reactions. Thus, the aim of this study is to investigate the influence of NADES with various molar compositions on the stability and structure of enzymes, applying molecular dynamics simulations. This can help to better understand the effect of individual compounds of NADES, in addition to eutectic mixtures. More specifically, we simulate the behavior of Candida antarctica lipase B (CALB) enzyme in NADES composed of choline chloride with either urea, ethylene glycol or glycerol. Hereto, we monitor the NADES microstructure, the general stability of the enzyme and changes in the structure of its active sites and surface residues. Our simulations show that none of the studied NADES systems significantly disrupt the microstructure of the solvent or the stability of the CALB enzyme within the time scales of the simulations. The enzyme preserves its initial structure, size and intra-chain hydrogen bonds in all investigated compositions and, for the first time reported, also in NADES with increased hydrogen bond donating compound ratios. As the main novelty, our results indicate that, in addition to the composition, the molar ratio can be an additional variable to fine-tune the physicochemical properties of NADES without altering the enzyme characteristics. These findings could facilitate the development and application of task-tailored NADES media for biocatalytic processes.