A systematic approach to identify cooperatively bound homotrimers

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysics

Background:

• Investigating cooperativity in molecular complexes is crucial for understanding biological processes.
• Existing computational methods like exhaustive or stochastic approaches can be computationally expensive.

Purpose of the Study:

• To present a systematic, multistage computational procedure for investigating cooperativity in trimeric molecular complexes.
• To offer an efficient alternative to exhaustive or stochastic computational methods.

Main Methods:

• Extraction of trimeric clusters from crystal structures.
• Gas-phase optimization and filtering using energetic and RMSD cutoffs.
• Computation of three-body interaction energies for low-energy conformations.

Main Results:

• The computational procedure was validated on 20 molecular crystals from the Cambridge Structural Database.
• 25% of tested structures yielded gas-phase homotrimers exhibiting cooperative binding energy.
• The calculations were performed at the BP86-D3(BJ)/def2-SVP//TPSS-D3(BJ)/def2-TZVP level of theory.

Conclusions:

• The developed multistage computational procedure is effective for studying cooperativity in trimeric complexes.
• The method provides a viable and potentially more efficient alternative to traditional computational strategies.
• Cooperative binding energy was demonstrated in a significant subset of tested homotrimers.