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

TL;DR

This paper introduces a computational method for estimating absolute free energies of molecules by assembling pre-calculated fragment libraries, significantly reducing calculation time and enabling efficient peptide free energy estimation.

Contribution

The method combines fragment libraries with staged growth calculations to efficiently estimate molecular free energies, validated against standard dynamics simulations.

Findings

Fragment libraries enable rapid free energy calculations.

The approach accurately estimates peptide free energies.

Equilibrium ensembles can be generated without extra computational cost.

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.