In silico alchemy: A tutorial for alchemical free-energy perturbation calculations with NAMD

This tutorial explains how NAMD and related tools can be used to setup and perform alchemical freeenergy simulations within the free-energy perturbation (FEP) theory. The force-field independent, “zero-sum” transformation of ethane into ethane is used as an introductory, prototypical example. FEP is then used to compute the free energy of charging a naked Lennard-Jones particle into a sodium ion. Next, the variation in solvation free energy upon mutation of a tyrosine residue into alanine is examined in the Ala–Tyr–Ala tripeptide. Last, the concept of standard binding free energy is illustrated in the simple case of a potassium ion binding a ionophore, 18–crown–6. Prior knowledge of NAMD and standard molecular dynamics simulations is assumed. c © 2010, Centre National de la Recherche Scientifique, University of Illinois, Urbana–Champaign