Modeling binding pathways can provide insight into molecular recognition, including kinetic mechanisms, barriers to binding, and gating effects. We will present a novel computational approach, Hopping Minima, for the determination of conformational transitions of single molecules as well as binding pathways for molecular complexes. The method begins by thoroughly sampling a set of conformational minima for a molecular system. The natural motions of the system are modeled using the normal modes of the sampled minima and multiple minima are finally combined to form binding pathways for molecular complexes. We will discuss our model systems, alanine dipeptide and a set of chemical host-guest systems: two cryptophane hosts with two guest cations, trimethylammonium and tetramethylammonium. We also discuss the energetic information along a binding pathway. This approach has advantages over simulation-based methods for studying systems with slow binding processes and can help design molecules with preferred binding kinetics.

Efficient method to elucidate ligand binding pathways: Binding kinetics studies for cryptophane host-guest complexes

246th National Meeting (2013)

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