Atomistically modeling the chemical potential of small molecules in dense systems

We test a simple grid-search method, in combination with the usual Widom test-particle insertion procedure, to enhance the efficiency of the latter for dense liquids that consist of small molecules. We use simple-point-charge/extended water at different temperatures as an example to illustrate the various aspects that affect the performance. Speed-up factors of up to 100 allow the excess chemical potential to be computed in this very dense system while maintaining the basic simplicity of Widom's method.