Binding and hydrolysis of ampicillin are described in a model active site derived from dinuclear B. fragilis zinc lactamase. The protein binding site consists of the two zinc cations bound with a bridging hydroxide and ligands from the first-shell residues, conserved residues near the zinc site, and the moveable loop of residues from numbers 43-53. The model active site consists of the first-shell residues, the conserved residues, and glu45 and glu47 from the moveable loop. Ampicillin is primarily located in the active site by the binding of the thiazolidine ring's extra-cyclic carboxylate to the ammonium of conserved lysine 184 when water bound to Zn2 in the active site is retained. A comparable strong salt bridge is formed between the ammonium of the ampicillin zwitterion and glu45 on the flexible loop that moves mostly as a unit at least 10 A to complete the binding site. The zwitterion character of this antibiotic influences the final docking arrangement and ultimate reaction path. Classical molecular dynamics, in the presence of Zn2 bound water, Watt and Wat2, and a limited number of waters placed around the ionic groups in the active site, determined a number of reactive docking conformations. One of the low-energy structures with strong interactions to glu45 and glu47 was chosen by the reactive proximity of the nucleophilic water, Wat2, to calculate the reaction path for binding reactant, intermediates, and product for the initial hydrolysis reaction. Water is added to solvate the classical reactant structure, and the reaction path was calculated quantum mechanically within a model chosen from the molecular mechanics structure. Two waters were found in a productive conformation for hydrolysis, the water bound to Zn2 (path 1) and water bound to the ampicillin carboxylate (path 2). In path 1, the hydrolysis product is only bound to the enzyme through hydrogen bonds and can be released by solvating these bonds. Additional proton-transfer steps from the initial product can occur, however, to create intermediates from this product stabilized by interaction with the Zn1 cation. The product formed in path 2 is bound directly to Zn2 suggesting that neither zinc is specially chosen for a catalytic role. Within this model the entire active site is utilized for both binding and catalysis in the case of ampicillin. Strong polar hydrogen bonds are found to the substrate, the waters in the active site, and the residue ligands present in the active site. Autocatalysis or assistance in water activation by the carboxylate of the antibiotic is found and likely to be general. The proton abstracted from the water can park on a number of anionic or polar atom sites in the active site leading to a range of intermediates. The lactam ring C-N bond does not break with prior protonation of the nitrogen or with the initial attack by the hydroxide abstracted from the nucleophilic water but requires attack of the hydroxide at the carbonyl carbon either prior to proton binding or concurrently. This study provides insight into a wider variety of antibiotic docking and shows that more than one reaction path is possible within the highly ionic active site of a bimetallic lactamase.