A systematic approach to identify cooperatively bound homotrimers.

A systematic multistage computational procedure is presented to investigate cooperativity within trimeric molecular complexes. It is an alternative to exhaustive or stochastic-based approaches. Trimeric clusters were extracted from known crystal structures and optimized in the gas phase, and subsequently filtered using energetic and RMSD structural cutoffs. Three-body interaction energies were computed for the subset of distinct low-energy trimer conformations. The procedure was validated using a set of 20 molecular crystals taken from the Cambridge Structural Database, and 25% of these strucutres gave rise to gas-phase homotrimers that showed a cooperative binding energy at the BP86-D3(BJ)/def2-SVP//TPSS-D3(BJ)/def2-TZVP level of theory.