# WATER-TOLUENE (ΔG_toluene - ΔG_water) TRANSFER FREE ENERGY PREDICTIONS
#
# This file will be automatically parsed. It must contain the following four elements:
# predictions, name of method, software listing, and method description.
# These elements must be provided in the order shown with their respective headers.
#
# Any line that begins with a # is considered a comment and will be ignored when parsing.
#
# 
# PREDICTION SECTION
#
# It is mandatory to submit water to toluene (ΔG_toluene - ΔG_water) transfer free energy (TFE) predictions for all 16 molecules.
# Incomplete submissions will not be accepted.
# The energy units must be in kcal/mol.

# Please report the general molecule `ID tag` in the form of `SAMPL9-XX` (e.g. SAMPL9-1, SAMPL9-2, etc).
# Please report TFE standard error of the mean (SEM) and TFE model uncertainty.
#
# The data in each prediction line should be structured as follows:
# ID tag, TFE, TFE SEM, TFE model uncertainty
#
# If you use a microstate other than the challenge provided microstate, please note SMILES strings of microstates you used in your submission, such as in the methods section.
#
# The list of predictions must begin with the 'Predictions:' keyword as illustrated here.
Predictions:
SAMPL9-1,1.26,0.5,1.5
SAMPL9-2,-2.35,0.5,1.5
SAMPL9-3,-6.50,0.5,1.5
SAMPL9-4,-8.70,0.5,1.5
SAMPL9-5,-4.13,0.5,1.5
SAMPL9-6,4.39,0.5,1.5
SAMPL9-7,-2.67,0.5,1.5
SAMPL9-8,9.47,0.5,1.5
SAMPL9-9,-7.01,0.5,1.5
SAMPL9-10,-2.46,0.5,1.5
SAMPL9-11,13.48,0.5,1.5
SAMPL9-12,2.62,0.5,1.5
SAMPL9-13,-0.36,0.5,1.5
SAMPL9-14,-0.73,0.5,1.5
SAMPL9-15,10.25,0.5,1.5
SAMPL9-16,1.60,0.5,1.5
#
#
#
# Please list your name, using only UTF-8 characters as described above. The "Participant name:" entry is required.
Participant name:
Andrew Paluch
Sergio Rodriguez
Lucas Paul
Geradius Deogratias

#
#
# Please list your organization/affiliation, using only UTF-8 characters as described above.
Participant organization:
Miami University
Universidad Nacional de Santiago del Estero
Dar es Salaam University College of Education
University of Dar es Salaam

#
#
# NAME SECTION
#
# Please provide an informal but informative name of the method used.
# The name must not exceed 40 characters.
# The 'Name:' keyword is required as shown here.
Name:
sm8-tfe-multiple-conformations-basis

#
#
# COMPUTE TIME SECTION
#
# Please provide the average compute time across all of the molecules.
# For physical methods, report the GPU and/or CPU compute time in hours.
# For empirical methods, report the query time in hours.
# Create a new line for each processor type.
# The 'Compute time:' keyword is required as shown here.
Compute time:
3, CPU

#
# COMPUTING AND HARDWARE SECTION
#
# Please provide details of the computing resources that were used to train models and make predictions.
# Please specify compute time for training models and querying separately for empirical prediction methods.
# Provide a detailed description of the hardware used to run the simulations.
# The 'Computing and hardware:' keyword is required as shown here.
Computing and hardware:
All electronic structure calculations were performed on the Pitzer Cluster at the Ohio Supercomputer Center 
(https://www.osc.edu/resources/technical_support/supercomputers/pitzer). 
The reported compute time is taken as the walltime times the number of processors (core hours). 
All of the electronic structure calculations used 20 cores.
Pitzer has a mix of processors. We did not specify the processor type upon submission, so a mix was used.  
The original Pitzer cluster was installed in late 2018 and is a Dell-built, Intel Xeon Skylake processor-based supercomputer with 260 nodes.
In September 2020, OSC installed an additional 398 Intel Xeon Cascade Lake processor-based 
nodes as part of a Pitzer Expansion cluster. 

# SOFTWARE SECTION
#
# List all major software packages used and their versions.
# Create a new line for each software.
# The 'Software:' keyword is required.
Software:
QChem/5.4.2

# METHOD CATEGORY SECTION
#
# State which method category your prediction method is better described as:
# `Physical (MM)`, `Physical (QM)`, `Empirical`, or `Mixed`.
# Pick only one category label.
# The `Category:` keyword is required.
Category:
Physical (QM)

# METHOD DESCRIPTION SECTION
#
# Methodology and computational details.
# Level of details should be roughly equivalent to that used in a publication.
# Please include the values of key parameters with units.
# Please explain how statistical uncertainties were estimated.
#
# If you have evaluated additional microstates, please report their SMILES strings and populations of all the microstates in this section.
# If you used a microstate other than the challenge provided microstate (`SMXX_micro000`), please list your chosen `Molecule ID` (in the form of `SMXX_extra001`) along with the SMILES string in your methods description.
#
# Use as many lines of text as you need.
# All text following the 'Method:' keyword will be regarded as part of your free text methods description.
Method:
Solvation free energy calculations were performed using electronic structure calculations using the SM8 continuum
solvation model in water and toluene. All calculations were performed using QChem/5.4.2.
Single point energy calculations were all performed at the M062X/6-31G* level of theory/basis in water and toluene.
A second set of calculations was then performed using M062X/6-31+G**

Starting with the SMILES provided by the challenge organizers, for each molecule we generated up to 50 low energy
conformations using Frog2 (https://bioserv.rpbs.univ-paris-diderot.fr/services/Frog2/), which were minimized
using the AMMOS force field. All of the conformations were generated using the free online server.

We then took the structures as generated by Frog2 and performed the necessary single point energy 
calculations in SM8 water and toluene using QChem/5.4.2. In each solvent QChem reports the 
free energy. Using all possible conformations, the computed energies were Boltzmann-weighted to obtain
an estimate of the free energy in each solvent, which was subsequently used to compute the transfer free energy.

By avoiding geometry optimizations using electronic structure calculations, the calculations were extremely
efficient.

The uncertainty in the solvation free energy calculations was taken to be 0.5 kcal/mol. Given a fixed geometry,
the computed single point energy calculations should remain unchanged. The error estimate is due to generation
of conformations. To obtain the model uncertainty,
we additionally performed calculation in 1-octanol which were used to generate an estimate of
logP octanol/water and the transfer free energy. This was then compared to reference logP values
obtained from DrugBank.ca, which were converted to transfer free energies.

For each molecule, between M062X/6-31G* and M062X/6-31+G** we selected the transfer free energy
that resulted in the best agreement with the reference octanol/water partition coefficient.
This decreased the error by approximately 0.8 log units.

#
#
# All submissions must either be ranked or non-ranked.
# Only one ranked submission per participant is allowed.
# Multiple ranked submissions from the same participant will not be judged.
# Non-ranked submissions are accepted so we can verify that they were made before the deadline.
# The "Ranked:" keyword is required, and expects a Boolean value (True/False)
Ranked:
True