Computational strategies of 12 binding free energies.

We performed MM calculations (MM energy minimization) or MD simulations of a complex, a protein, and a ligand, and evaluated 12 types of binding free energies by combining the respective coordinate sets. The enthalpy contributions of Gprotein and Gligand in equation 2 were calculated in the following two ways: (1) by using the coordinate sets of a protein (or ligand) obtained from the MD simulations (or MM calculations) of the protein (or ligand) and (2) by using the coordinate sets extracted from the MD simulation of a complex. Similar to the enthalpy contribution, the entropy contribution was also calculated by combining the respective MD coordinate sets. H indicates the sum of <EMM>, <GPB>, and <GSA> in equation 3, and TS indicates the entropy term in equation 3. MD COMPLEX (TSCOMPLEX), MDPROTEIN (TSPROTEIN), and MDLIGAND (TSLIGAND) denote the use of MD coordinate sets for a complex, protein, and ligand, respectively. Similarly, MMCOMPLEX, MMPROTEIN, and MMLIGAND denote the use of MM coordinate sets for a complex, protein, and ligand, respectively.