A key aspect necessary to computational drug design efforts is a detailed and physically accurate accounting of the interactions between a ligand and aqueous phase surroundings.  Additionally, such an accounting needs to be highly efficient in order to be practical.  Motivated by recent successes in accurate treatment of solvation with explicit representations of water, we have developed an efficient implicit model that encodes the detailed solvation response of explicit simulations that we call Semi-Explicit Assembly.  We discuss recent  extensions to and developments of this approach.  Of principal interest is the solvation of ligands with particularly strong interactions with their environments.  We outline the limitations of the existing method and show how one can treat such problematic molecules with greater accuracy, this while maintaining or even improving the computational efficiency.

Testing and assembling the response of water at molecular interfaces

244th National Meeting (2012)

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