Predictions:
SAMPL9-1,-3.6,1.5,1.3
SAMPL9-2,-5.7,1.7,1.3
SAMPL9-3,-3.2,1.9,1.3
SAMPL9-4,-5.5,2,1.3
SAMPL9-5,-3.7,2.3,1.3
SAMPL9-6,-0.6,1.9,1.3
SAMPL9-7,-7.4,1.5,1.3
SAMPL9-8,-4.6,2.6,1.3
SAMPL9-9,0.1,1.8,1.3
SAMPL9-10,-2.9,2,1.3
SAMPL9-11,0.2,4,1.3
SAMPL9-12,-1.2,3.3,1.3
SAMPL9-13,-3,2.6,1.3
SAMPL9-14,-6.3,2.8,1.3
SAMPL9-15,0.3,3.1,1.3
SAMPL9-16,-2.8,1,1.3


Participant name:
Hafiz Saqib Ali
Richard Henchman


Participant organization:
The University of Oxford
The University of Sydney


Name:
EE-MCC/GAFF2-AM1-BCC/TIP3P/MD/


Compute time:
4.00 h


Computing and hardware:
NVIDIA GPU CLUSTER


Software:
Amber 2020
AmberTools 22
CodeEntropy



Category:
Physical (MM)



Method:
Amber Tools 22 was used to create the topology and coordinate files of each system. Force-field parameters for the drug molecules and toluene were taken from the second generation of General AMBER Force Field (GAFF2) with partial charges derived using the AM1-BCC method as implemented in Antechamber. Four kinds of MD simulation were set up: (i) 1500 water molecules, (ii) 500 toluene molecules, (iii) each drug molecule solvated in 1500 water molecules, and (iv) each drug molecule solvated in 500 toluene molecules. All simulation boxes are cubic with side 36 angstroms. All simulations were carried out with Particle Mesh Ewald Molecular Dynamics (PMEMD) module of AMBER 20 package. For equilibration, each system was minimized for 2000 steps of steepest-descent minimization and heated gradually from 0 to 298.15 K for 200 ps of NVT molecular dynamics simulation using Langevin thermostat, with the collusion frequency of 5 ps–1, followed by 1 ns of NPT simulation using using Berendsen barostate. Furthermore, three repeats of 200 ns NPT MD simulations have been carried out using a 2 fs time step, the SHAKE protocol on hydrogen atoms and 10 Å non-bonded cut-off with periodic boundary conditions, and coordinates saved every 100 ps to give 2000 frames per simulation. Toluene-water logP values were calculated using the Energy-Entropy (EE) method which calculates the free energy of each system from the energy and entropy from the simulation. The free energy of the drug in toluene and pure water minus the free energy of the drug in water and pure toluene.  Energies were taken as the average simulation potential and kinetic energy. Entropies of the solute and first-shell solvent were calculated using Multiscale Cell Correlation (MCC) (10.3390/e21080750, https://doi.org/10.1007/s10822-021-00406-5, https://doi.org/10.1007/s10822-021-00401-w). Calculation of all necessary terms was done using in-house C++ code and the CodeEntropy software (https://codeentropy.readthedocs.io/en/latest/) from the force and coordinate trajectories in each simulation.



Ranked:
True