Absolute Aqueous Solvation Free Energy

Absolute Aqueous Solvation Free Energy

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

Get started How to run it

Absolute Aqueous Solvation Free Energy calculates how favorably one molecule moves from a vacuum into water, reported as a solvation free energy, ΔG_solv, in kcal/mol. This is also called the hydration free energy.

A more negative ΔG_solv means the molecule prefers to be in water, so it is more water loving. A value closer to zero, or positive, means the molecule prefers vacuum or an oily environment, so it is more water avoiding.

Under the hood it runs an alchemical free energy simulation: the molecule is gradually switched off from its surroundings once in plain water 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 water, for example to compare the water affinity of different compounds, to sanity check a force field, or as a building block in a larger property workflow. If you want the free energy of moving between two solvents instead of water versus vacuum, use Solvent Transfer Free Energy. For a non water solvent, use Absolute Nonaqueous Solvation Free Energy.

Inputs

Provide exactly one of smiles or helm.

Input	Required	What it is
smiles	one of smiles or helm	SMILES string of the molecule.
helm	one of smiles or helm	HELM2 notation for a peptide, for example PEPTIDE1{A.G.F.K.L}$$$$V2.0. Supports cyclic, disulfide, lactam, D amino acids, N methylated, and non canonical residues.
conformer_method	no, default etkdg	3D shape generator used only for HELM input. etkdg is fast, xtb is slower but gives better geometries. Ignored for SMILES input.
assign_protonation_states	no, default true	Protonates the molecule 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 water.
solvent_prod_length	no, default 0.4 ns	Production length per replica, in water.
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 repeats used for the uncertainty estimate. More repeats give a smaller uncertainty.
keep_dirs	no, default true	Preserves the full simulation outputs so you can download them.

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

How to run it

Submit your own molecule 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 Aqueous Solvation Free Energy from the tools list, then on the Inputs and Parameters step enter the molecule as a SMILES string (or a peptide as HELM), 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="aqueous_solvation",
    input_data={
        "smiles": "CCO",
        "ph": 7.0,
        "protocol_repeats": 3,
    },
)

From the CLI

Pass the inputs as a JSON string.

opal jobs submit --job-type aqueous_solvation \
  --input-data '{"smiles": "CCO", "ph": 7.0, "protocol_repeats": 3}'

Reading the result

The main output is dg_solvation, the solvation free energy ΔG_solv, 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 water. 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. Small, neutral molecules converge quickly; charged or flexible molecules need more sampling.