GRAVY

(1.0.0)

Calculate average protein hydropathy and classify sequences as hydrophobic or hydrophilic.

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What is GRAVY?

GRAVY (Grand Average of Hydropathy) is a fundamental metric for quantifying the overall hydrophobicity or hydrophilicity of a protein sequence.

Introduced by Jack Kyte and Russell Doolittle in their seminal 1982 paper, this index has become one of the most widely used protein parameters in protein science.

The GRAVY score provides rapid insight into a protein's solubility, membrane association, and folding behavior. A positive value indicates a hydrophobic protein, while a negative value indicates a hydrophilic protein.

How does GRAVY work?

GRAVY is calculated by summing the hydropathy values of all amino acids in a sequence and dividing by the sequence length:

GRAVY = \frac{1}{N} \sum_{i=1}^{N} h_i

Where $N$ is the total number of amino acids and $h_i$ is the hydropathy value of amino acid $i$ . This simple arithmetic mean yields a single value that characterizes the entire protein's hydropathic character.

The Kyte-Doolittle hydropathy scale

The calculation uses experimentally derived hydropathy values for each amino acid. These values, ranging from +4.5 (most hydrophobic) to -4.5 (most hydrophilic), were determined by combining water-vapor transfer free energies with solvent accessibility data from crystal structures.

Amino Acid	Value	Amino Acid	Value
Ile (I)	4.5	Gly (G)	-0.4
Val (V)	4.2	Ser (S)	-0.8
Leu (L)	3.8	Trp (W)	-0.9
Phe (F)	2.8	Tyr (Y)	-1.3
Cys (C)	2.5	Pro (P)	-1.6
Met (M)	1.9	His (H)	-3.2
Ala (A)	1.8	Glu (E)	-3.5
Thr (T)	-0.7	Gln (Q)	-3.5
Asn (N)	-3.5	Asp (D)	-3.5
Lys (K)	-3.9	Arg (R)	-4.5

Interpreting the GRAVY results

The GRAVY score directly correlates with protein solubility and membrane interaction potential:

GRAVY < -0.5: Highly hydrophilic, typically soluble cytoplasmic or secreted proteins
GRAVY -0.5 to 0.5: Moderate hydropathy, common for globular proteins
GRAVY > 0.5: Hydrophobic, potential membrane association
GRAVY > 1.0: Strongly hydrophobic, often insoluble or membrane-embedded

Most soluble proteins have negative GRAVY scores. Transmembrane proteins and membrane-associated domains typically show positive values due to their enrichment in hydrophobic residues.

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