Absolute Nonaqueous Solvation Free Energy

Absolute Nonaqueous Solvation Free Energy

Predict how favorably a single molecule dissolves in an organic solvent, on an absolute scale.

Get started How to run it

Absolute Nonaqueous Solvation Free Energy calculates how favorably one molecule moves from a vacuum into an organic (non water) solvent, reported as a solvation free energy, ΔG_solv, in kcal/mol. You pick the solvent, for example ethanol, methanol, hexane, or DMSO.

A more negative ΔG_solv means the molecule prefers to be in that solvent. A value closer to zero, or positive, means it prefers vacuum.

Under the hood it runs an alchemical free energy simulation: the molecule is gradually switched off from its surroundings once in the chosen solvent and once in vacuum, and the difference between those two gives the solvation free energy.

When to use it

Use it when you want an absolute measure of how well a molecule dissolves in a specific organic solvent. This is useful for formulation work, for understanding behaviour in non aqueous media, or as one half of a transfer comparison. For water specifically, use Absolute Aqueous Solvation Free Energy. To compare two solvents directly in one job, use Solvent Transfer Free Energy.

Inputs

Provide exactly one of smiles_solute or helm.

Input	Required	What it is
smiles_solute	one of smiles_solute or helm	SMILES string of the solute, the molecule you are dissolving.
helm	one of smiles_solute or helm	HELM2 notation for a peptide solute, for example PEPTIDE1{A.G.F.K.L}$$$$V2.0.
conformer_method	no, default etkdg	3D shape generator used only for HELM input. etkdg is fast, xtb is slower but better. Ignored for SMILES input.
smiles_solvent	yes	SMILES string of the organic solvent, for example CCO for ethanol, CO for methanol, CCCCCC for hexane, or CS(=O)C for DMSO.
assign_protonation_states	no, default true	Protonates the solute automatically at the given pH. Turn off if your input is already protonated.
ph	no, default 7.0	pH used to decide protonation.
solvent_equil_length	no, default 0.08 ns	Equilibration length per replica, in the solvent.
solvent_prod_length	no, default 0.4 ns	Production length per replica, in the solvent.
vacuum_equil_length	no, default 0.08 ns	Equilibration length per replica, in vacuum.
vacuum_prod_length	no, default 0.4 ns	Production length per replica, in vacuum.
platform	no, default CUDA	Compute platform, one of CUDA, OpenCL, CPU, or Reference.
protocol_repeats	no, default 3, minimum 1	Number of independent replicas. The reported uncertainty combines the per replica uncertainty with the spread between replicas.
keep_dirs	no, default false	Preserves the scratch and output directories so you can download them. Leave off to save storage.

Longer simulation lengths and more repeats give more reliable numbers, but cost more runtime and credits.

How to run it

Submit your own molecule and solvent from Azulene Studio, the Python SDK, or the CLI. New here? The Get started page walks through installing, logging in, and running a ready made example first.

In Azulene Studio

Open Absolute Nonaqueous Solvation Free Energy from the tools list, then on the Inputs and Parameters step enter the solute as a SMILES string (or a peptide as HELM) and the solvent as a SMILES string, adjust the pH and simulation lengths if you want, then Review and Submit.

From the Python SDK

from opal import jobs

result = jobs.submit(
    job_type="nonaqueous_solvation",
    input_data={
        "smiles_solute": "CCO",
        "smiles_solvent": "CO",
        "protocol_repeats": 3,
    },
)

From the CLI

Pass the inputs as a JSON string.

opal jobs submit --job-type nonaqueous_solvation \
  --input-data '{"smiles_solute": "CCO", "smiles_solvent": "CO", "protocol_repeats": 3}'

Reading the result

The main output is dg_solvation, the solvation free energy ΔG_solv in the chosen solvent, reported with an uncertainty, a dg_solvation_unit (kcal/mol), and an uncertainty_unit. In Azulene Studio this shows as a single hero number labelled “ΔG solvation”. The input molecule is echoed back in smiles.

A more negative dg_solvation means the molecule dissolves more favorably in that solvent. More protocol_repeats lower the uncertainty. If keep_dirs is on, the full simulation outputs can be downloaded, along with per replica mixing statistics under replica_transition_statistics.

Notes

Keep the simulation lengths short for a quick first run. For reliable numbers, use longer production lengths and at least 3 repeats. This tool runs on a GPU, and runtime grows with the simulation lengths and the number of repeats. The solvent must be given as a SMILES string, not a name.