Table 2.
Summary of predictions submitted for the SAMPL3 host-guest binding affinity challenge.
| ID | Method (e/p)a | Pot. Energy | Charges | Solv. | Conf. | Config. Entropy |
RMSE | R2 |
|---|---|---|---|---|---|---|---|---|
| Host1 | ||||||||
| 1 | SIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 1.6 | 0.42 |
| 2 | SIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 1.9 | 0.44 |
| 3 | SIE (e) | GAFF | AM1-BCC | FiSH | Docking | None | 6.4 | 0.22 |
| 4 | rSIE (e) | GAFF | AM1-BCC | FiSH | Docking | None | 2.0 | 0.22 |
| 5 | SIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 1.5 | 0.40 |
| 5* | rSIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 2.8 | 0.40 |
| 6 | MM/GBSA (e) | GAFF | AM1-BCC | GBSA | MD/Expl. | RRHO | 31.9 | 0.58 |
| 7 | MM/PBSA (e) | GAFF | AM1-BCC | PBSA | MD/Expl. | RRHO | 23.4 | 0.80 |
| 8 | Szybki (e) | MMFF94 | AM1-BCC | Szybki | Docking | RRHO | 3.1 | 0.19 |
| 9 | M2 (e) | CHARMm | Vcharge | PBSA | Tork | HA/MS | 7.5 | 0.24 |
| 10 | BEDAM (p) | OPLS | OPLS | AGBNP2 | MD/Imp. | Implicit | 2.5 | 0.49 |
| 11 | TI/BAR (p) | CGenFF | CGenFF | TIP3P | MD | Implicit | 2.6 | 0.01 |
| 12 | TI (p) | GAFF | RESP | TIP3P | MD | Implicit | 3.6 | 0.51 |
| 13 | Wang-Landau (p) | GAFF | AM1-BCC | TIP3P | MD | Implicit | 4.0 | 0.34 |
| 14 | FEP/OSRW (p) | GAFF | AM1-BCC | TIP3P | MD | Implicit | 11.3 | 0.81 |
| Host2/Host3 | ||||||||
| 1 | SIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 1.4 | 0.77 |
| 2 | SIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 1.4 | 0.77 |
| 3 | SIE (e) | GAFF | AM1-BCC | FiSH | Docking | None | 5.1 | 0.44 |
| 4 | rSIE (e) | GAFF | AM1-BCC | FiSH | Docking | None | 1.5 | 0.46 |
| 5 | SIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 1.4 | 0.77 |
| 5* | rSIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 1.9 | 0.79 |
| 6 | MM/GBSA (e) | GAFF | AM1-BCC | GBSA | MD/Exp. | RRHO | 45.2 | 0.57 |
| 7 | MM/PBSA (e) | GAFF | AM1-BCC | PBSA | MD/Exp. | RRHO | 14.8 | 0.14 |
| 8 | Szybki (e) | MMFF94 | AM1-BCC | Szybki | Docking | RRHO | 3.1 | 0.77 |
| 9 | M2 (e) | CHARMm | Vcharge | PBSA | Tork | HA/MS | 4.1 | 0.80 |
| 15 | MM/PBSA (e) | MMFF94 | AM1-BCC | PBSA | Docking | RRHO | 7.5 | 0.93 |
| 16 | MM/PBSA (e) | MMFF94 | AM1-BCC | PBSA | Docking | RRHO | 5.2 | 0.92 |
| 17 | DFT/PCM (e) | B3LYP | -- | PCM | Docking | None | 3.0 | 0.64 |
| 18 | DFT/PCM (e) | B3LYP | -- | PCM | Docking | RRHO | 5.9 | 0.94 |
| Hosts 1/2/3 | ||||||||
| 1 | SIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 1.5 | 0.51 |
| 2 | SIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 1.7 | 0.53 |
| 3 | SIE (e) | GAFF | AM1-BCC | FiSH | Docking | None | 6.0 | 0.27 |
| 4 | rSIE (e) | GAFF | AM1-BCC | FiSH | Docking | None | 1.8 | 0.27 |
| 5 | SIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 1.5 | 0.50 |
| 5* | rSIE (e) | GAFF | AM1-BCC | PBSA | Docking | None | 2.5 | 0.50 |
| 6 | MM/GBSA (e) | GAFF | AM1-BCC | GBSA | MD/Expl. | RRHO | 37.3 | 0.24 |
| 7 | MM/PBSA (e) | GAFF | AM1-BCC | PBSA | MD/Expl. | RRHO | 20.7 | 0.29 |
| 8 | Szybki (e) | MMFF94 | AM1-BCC | Szybki | Docking | RRHO | 3.1 | 0.26 |
| 9 | M2 (e) | CHARMm | Vcharge | PBSA | Tork | HA/MS | 6.5 | 0.02 |
The basic approach, end-point (e) or pathway (p), is indicated in parentheses next to the name of each method. Abbreviations: MD/Expl. -- Molecular dynamics simulation with explicit water model. SIE - Solvated interaction energy; rSIE – Rescaled SIE; GAFF - Generalized AMBER force field; AM1- Austin Model 1; BCC - Bond charge correction; PBSA - Poisson-Boltzmann Surface Area; FiSH - First-shell hydration; GBSA - Generalized-Born Surface Area; MM - Molecular mechanics; MD - Molecular dynamics; RRHO - Rigid rotor harmonic oscillator; M2 - Mining Minima; BEDAM - Binding energy distribution analysis method; HA/MS - Harmonic approximation/Mode scanning; MMFF - Merck molecular force field; CHARMM - Chemistry at Harvard molecular mechanics; TI - Thermodynamic integration; BAR - Bennett acceptance ratio; CGenFF - CHARMM generalized force-field; FEP - Free energy pertubation; OSRW - Orthogonal space random walk; OPLS - Optimized potentials for liquid simulations; AGBNP2 - Analytical Generalized Born plus non-polar 2; RESP - Restrained electrostatic potential; PCM - Polarizable continuum model; DFT - Density functional theory; B3LYP - Becke, three-parameter, Lee-Yang-Parr.
Despite the methodological differences, submission 5* is effectively a linear scaling of submission 5 (R2 = 0.998), with a scaling coefficient of 0.41 and an offset of −2.90 kcal/mol.