Table 1.

The configurational entropy calculation for binding of compound 1 to bacteriophage T4 lysozyme using the RR approach.^a

Protein	1	2	3	4	5	6	7	8
RR10→0.003	−5.47	−5.55	−5.44	−5.35	−5.69	−5.6	−5.88	−5.46
RR1→0.003	−3.91	−3.55	−3.2	−3.02	−4.18	−3.9	−3.29	−3.06
RR0.3→0.003	−2.5	−2.09	−2.15	−1.95	−2.78	−2.53	−2.3	−2.14
RR0.03→0.003	−0.76	−0.64	−0.6	−0.61	−0.64	−0.6	−0.96	−0.62
QH10	−5.7	−5.5	−5.42	−5.61	−5.24	−5.79	−5.66	−5.6
RR10→0.003+ QH10	−11.17	−11.05	−10.86	−10.96	−10.93	−11.39	−11.54	−11.06
Water
RR10→0.003	−11.71	−12.03	−12.06	−12.37	−10.6	−12.98	−10.63	−12.26
RR1→0.003	−9.44	−9.77	−9.83	−10.12	−9.27	−10.51	−9.15	−9.96
RR0.3→0.003	−6.97	−7.23	−7.35	−7.53	−6.76	−7.99	−6.63	−7.5
RR0.03→0.003	−2.56	−2.64	−2.6	−3.41	−2.49	−3.34	−2.75	−2.61
QH10	−6.27	−6.24	−5.87	−5.68	−5.77	−6.5	−5.51	−6.36
RR10→0.003+ QH10	−17.98	−18.27	−17.93	−18.05	−16.37	−19.48	−16.14	−18.62
–T ΔScalc	5.28

^aEnergy values are given in kcal/mol. The table includes the results from eight sets (1–8) of simulations with different restraint coordinates. The simulations consisted of 41 windows, each with a simulation time of 40ps at 300K with 1fs time step. The value in bold signifies the best estimate of –TΔS obtained by taking the corresponding values from the run with R that gives the smallest |ΔG'| and thus, the value that satisfies Eq. 9. As discussed in the main text, this variational minimization reflects the fact that all the RR free energies contain enthalpic contributions and these contributions approach zero for restraint coordinates that gives the lowest RR contribution.