Protein aggregation has been observed inside cells and holds true for membraneless organdies. The precise understanding of protein dimerization is a prerequisite for manipulating protein aggregation, which is promising for elevating enzyme concentration to enhance their catalytic performance. Here, the dimerization of two industrially important enzymes of cytochrome P450 (P450) and organophosphorus hydrolase (OPH) is investigated using all-atom explicit solvent molecular dynamics simulations, umbrella sampling, and protein-protein docking calculations. The calculated potentials of mean force of dimer-monomer dissociation demonstrate that the dimeric forms are more stable with the free energy barrier of around 60 kJ/mol for P450 and 101 kJ/mol for OPH. The docking calculations on the OPH dimer evidence the uniqueness of the native orientation. The protein dimers form "mirror"-like orientations with some degree of rotation. Such signature orientations are interpreted based on the predominant polar amino acids in the contact regime. In the dimer conformations, the active sites are exposed. This work highlights the crucial roles of the polar and nonpolar protein surface domains to form enzymatically active protein dimer aggregates. Our work will potentially aid the design of molecules that can deliver and protect native protein function in various environments.