Absolute free energies estimated by combining pre-calculated molecular fragment libraries

Abstract

The absolute free energy -- or partition function, equivalently -- of a molecule can be estimated computationally using a suitable reference system. Here, we demonstrate a practical method for staging such calculations by growing a molecule based on a series of fragments. Significant computer time is saved by pre-calculating fragment configurations and interactions for re-use in a variety of molecules. We employ such fragment libraries and interaction tables for amino acids and capping groups to estimate free energies for small peptides. Equilibrium ensembles for the molecules are generated at no additional computational cost, and are used to check our results by comparison to standard dynamics simulation.