Experimental and predicted binding free energies of small molecules binding to bacteriophage T4 lysozyme. Prediction methods include TI, LIE, umbrella sampling (US) and molecular mechanics Poisson-Boltzmann (generalized Born)/surface area (MM-PB(GB)/SA)
| . | . | Predicted |$\Delta\Delta G_{bind}^{[b]}$| (computational costs|$^{[c]}$|) . | ||||
|---|---|---|---|---|---|---|
| Ligand pair (formula) . | Experimental |$\Delta\Delta G_{bind}^{[a]}$| . | TI . | LIE . | US . | MM-PB/SA . | MM-GB/SA . |
| benzene|$\rightarrow$|toluene (C6H6|$\rightarrow$|C7H8) | −0.32 | 0.02|$\pm$|0.14 (73.67) | −0.65|$\pm$|0.68 (3.57) | 6.05 (129.7) | −1.33|$\pm$|2.46 (3.25) | −3.09|$\pm$|1.97 (2.8) |
| benzene|$\rightarrow$|phenol (C6H6|$\rightarrow$|C6H6O) | |$>0$| | 1.35|$\pm$|0.44 (10.05) | −1.55|$\pm$|1.13 (3.58) | 7.15 (128.68) | 1.24|$\pm$|2.93 (3.26) | −0.62|$\pm$|2.20 (2.81) |
| . | . | Predicted |$\Delta\Delta G_{bind}^{[b]}$| (computational costs|$^{[c]}$|) . | ||||
|---|---|---|---|---|---|---|
| Ligand pair (formula) . | Experimental |$\Delta\Delta G_{bind}^{[a]}$| . | TI . | LIE . | US . | MM-PB/SA . | MM-GB/SA . |
| benzene|$\rightarrow$|toluene (C6H6|$\rightarrow$|C7H8) | −0.32 | 0.02|$\pm$|0.14 (73.67) | −0.65|$\pm$|0.68 (3.57) | 6.05 (129.7) | −1.33|$\pm$|2.46 (3.25) | −3.09|$\pm$|1.97 (2.8) |
| benzene|$\rightarrow$|phenol (C6H6|$\rightarrow$|C6H6O) | |$>0$| | 1.35|$\pm$|0.44 (10.05) | −1.55|$\pm$|1.13 (3.58) | 7.15 (128.68) | 1.24|$\pm$|2.93 (3.26) | −0.62|$\pm$|2.20 (2.81) |
[a]Calculated based on experimental |$K_d$| values. |$\Delta \Delta G_{bind}^{L\rightarrow L^{\prime}}=RT\ ln(\frac{K_d^{L\prime}}{K_d^L})$| with |$T=300$| K.
[b] In kcal/mol. |$K_d$||$\sigma_{\Delta\Delta G_{bind}^{L\rightarrow L\prime}}=\sqrt{\sigma_{\Delta G_{L\rightarrow L\prime}^{protein}}^2\pm\sigma_{\Delta G_{L\rightarrow L\prime}^{water}}^2}$| (TI) or |$\sigma_{\Delta\Delta G_{bind}^{L\rightarrow L\prime}}=\sqrt{\sigma_{\Delta G_{bind}^{L}}^2\pm\sigma_{\Delta G_{bind}^{L\prime}}^2}$| (LIE and MM-PB(GB)/SA).
[c]In hours. Calculated as the sum of simulation time and energy-estimation time.
[d]Entropy contributions not included
Experimental and predicted binding free energies of small molecules binding to bacteriophage T4 lysozyme. Prediction methods include TI, LIE, umbrella sampling (US) and molecular mechanics Poisson-Boltzmann (generalized Born)/surface area (MM-PB(GB)/SA)
| . | . | Predicted |$\Delta\Delta G_{bind}^{[b]}$| (computational costs|$^{[c]}$|) . | ||||
|---|---|---|---|---|---|---|
| Ligand pair (formula) . | Experimental |$\Delta\Delta G_{bind}^{[a]}$| . | TI . | LIE . | US . | MM-PB/SA . | MM-GB/SA . |
| benzene|$\rightarrow$|toluene (C6H6|$\rightarrow$|C7H8) | −0.32 | 0.02|$\pm$|0.14 (73.67) | −0.65|$\pm$|0.68 (3.57) | 6.05 (129.7) | −1.33|$\pm$|2.46 (3.25) | −3.09|$\pm$|1.97 (2.8) |
| benzene|$\rightarrow$|phenol (C6H6|$\rightarrow$|C6H6O) | |$>0$| | 1.35|$\pm$|0.44 (10.05) | −1.55|$\pm$|1.13 (3.58) | 7.15 (128.68) | 1.24|$\pm$|2.93 (3.26) | −0.62|$\pm$|2.20 (2.81) |
| . | . | Predicted |$\Delta\Delta G_{bind}^{[b]}$| (computational costs|$^{[c]}$|) . | ||||
|---|---|---|---|---|---|---|
| Ligand pair (formula) . | Experimental |$\Delta\Delta G_{bind}^{[a]}$| . | TI . | LIE . | US . | MM-PB/SA . | MM-GB/SA . |
| benzene|$\rightarrow$|toluene (C6H6|$\rightarrow$|C7H8) | −0.32 | 0.02|$\pm$|0.14 (73.67) | −0.65|$\pm$|0.68 (3.57) | 6.05 (129.7) | −1.33|$\pm$|2.46 (3.25) | −3.09|$\pm$|1.97 (2.8) |
| benzene|$\rightarrow$|phenol (C6H6|$\rightarrow$|C6H6O) | |$>0$| | 1.35|$\pm$|0.44 (10.05) | −1.55|$\pm$|1.13 (3.58) | 7.15 (128.68) | 1.24|$\pm$|2.93 (3.26) | −0.62|$\pm$|2.20 (2.81) |
[a]Calculated based on experimental |$K_d$| values. |$\Delta \Delta G_{bind}^{L\rightarrow L^{\prime}}=RT\ ln(\frac{K_d^{L\prime}}{K_d^L})$| with |$T=300$| K.
[b] In kcal/mol. |$K_d$||$\sigma_{\Delta\Delta G_{bind}^{L\rightarrow L\prime}}=\sqrt{\sigma_{\Delta G_{L\rightarrow L\prime}^{protein}}^2\pm\sigma_{\Delta G_{L\rightarrow L\prime}^{water}}^2}$| (TI) or |$\sigma_{\Delta\Delta G_{bind}^{L\rightarrow L\prime}}=\sqrt{\sigma_{\Delta G_{bind}^{L}}^2\pm\sigma_{\Delta G_{bind}^{L\prime}}^2}$| (LIE and MM-PB(GB)/SA).
[c]In hours. Calculated as the sum of simulation time and energy-estimation time.
[d]Entropy contributions not included
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