Force-field and quantum-mechanical binding study of selected SAMPL3 host-guest complexes.

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Supramolecular Chemistry

Background:

• Accurate prediction of host-guest binding energies is crucial for designing novel receptors and understanding molecular recognition.
• Classical and quantum mechanical methods are employed to model these interactions, but their accuracy varies.

Purpose of the Study:

• To evaluate the performance of the Merck molecular force field with Poisson-Boltzmann electrostatics (MMFF/PB) for estimating binding free energies.
• To assess the accuracy of density functional theory (DFT) with B3LYP/PCM for calculating binding enthalpies.
• To compare computational predictions with experimental calorimetry data for various host-guest systems.

Main Methods:

• Binding free energies were calculated using MMFF/PB for guest molecules (amines, benzimidazoles) complexed with cucurbituril hosts.
• Binding enthalpies were computed using DFT (B3LYP functional) with a polarizable continuum model (PCM).

Main Results:

• The MMFF/PB method generally provided reasonable agreement (±2 kcal/mol) with experimental binding free energies.
• Significant deviations were observed for three specific host-guest pairs using the MMFF/PB approach.
• DFT/PCM predictions for binding enthalpies showed large deviations (≥70%) compared to experimental calorimetry data.

Conclusions:

• MMFF/PB is a viable method for estimating host-guest binding energies, though limitations exist for certain systems.
• DFT/PCM, as applied here, demonstrated poor accuracy for predicting binding enthalpies in these host-guest complexes.
• The study highlights the importance of molecular models and intermolecular potentials in accurately simulating host-guest complexation.