This work shows that a deep-sea protein, 3LEZ, with known in vitro β-lactamase activity, proved stable, substantially in the conformation detected by X-ray diffraction of the crystal, when subjected to molecular-dynamics (MD) simulations under conditions compatible with shallow seas. Docking simulations showed that the β-lactamase active site S85 of 3LEZ (S70 in Ambler numbering) is the preferential binding pocket for not only β-lactam antibiotics and inhibitors, but, surprisingly, also for a wide variety of other biologically active compounds in various chemical classes, including marine metabolites. In line with the in vitro β-lactamase activity, a) affinities on docking β-lactam antibiotics and inhibitors onto 3LEZ were found to roughly parallel published Km and Ki values, obtained from MichaelisMenten kinetics under room conditions, and b) DFT calculations agreed with experiments that the irreversible reaction of the β-lactamase inhibitor clavulanic acid with the whole S85 catalytic center of 3LEZ is spontaneous. These observations must be viewed in the light that a) the compounds in other chemical classes showed comparable affinities, and, in some cases, even higher than β-lactams, for the S85 active site, b) Km and Ki data are not available at the high hydrostatic pressure of the deep sea, where 3LEZ is believed to have evolved, c) an inverse order of affinities for the β-lactams, with respect to both experimentation and simulations at room conditions, was observed from comparative docking simulations with 3LEZ derived from MD under high hydrostatic pressure. Although MD requires a general assessment for high hydrostatic pressure before c) above is given the same weight as all other observations, this work questions the conclusion that the in vitro determined β-lactamase activity represents the ecological role of 3LEZ.