Tables

Overview Table

All tables from the AAanalysis documentation are listed here, in chronological order based on the project history.

Table	Description	See Also
t1_overview_benchmarks	Protein benchmark datasets	aa.load_dataset
t2_overview_scales	Amino acid scale datasets	aa.load_scales
t3a_aaontology_categories	AAontology scale categories	aa.load_scales
t3b_aaontology_subcategories	AAontology scale subcategories	aa.load_scales

Protein Benchmark Datasets

Three types of benchmark datasets are provided:

• Residue prediction (AA): Datasets used to predict specific properties of amino acid residues.

• Domain prediction (DOM): Datasets used to predict specific properties of domains.

• Sequence prediction (SEQ): Datasets used to predict specific properties of sequences.

Datasets are named beginning with a classification (e.g., ‘AA_LDR’, ‘DOM_GSEC’, ‘SEQ_AMYLO’). Some datasets have an additional version for positive-unlabeled (PU) learning containing only positive (1) and unlabeled (2) data samples, as indicated by appending ‘_PU’ to the dataset name (e.g., ‘DOM_GSEC_PU’).

Level	Dataset	# Sequences	# Amino acids	# Positives	# Negatives	Predictor	Description	Reference	Label
Amino acid	AA_CASPASE3	233	185605	705	184900	PROSPERous	Prediction of caspase-3 cleavage site	Song18	1 (adjacent to cleavage site), 0 (not adjacent to cleavage site)
Amino acid	AA_FURIN	71	59003	163	58840	PROSPERous	Prediction of furin cleavage site	Song18	1 (adjacent to cleavage site), 0 (not adjacent to cleavage site)
Amino acid	AA_LDR	342	118248	35469	82779	IDP-Seq2Seq	Prediction of long intrinsically disordered regions (LDR)	Tang20	1 (disordered), 0 (ordered)
Amino acid	AA_MMP2	573	312976	2416	310560	PROSPERous	Prediction of Matrix metallopeptidase-2 (MMP2) cleavage site	Song18	1 (adjacent to cleavage site), 0 (not adjacent to cleavage site)
Amino acid	AA_RNABIND	221	55001	6492	48509	GMKSVM-RU	Prediction of RNA-binding protein residues (RBP60 dataset)	Yang21	1 (binding), 0 (non-binding)
Amino acid	AA_SA	233	185605	101082	84523	PROSPERous	Prediction of solvent accessibility (SA) of residue (AA_CASPASE3 data set)	Song18	1 (exposed/accessible), 0 (buried/non-accessible)
Sequence	SEQ_AMYLO	1414	8484	511	903	ReRF-Pred	Prediction of amyloidognenic regions	Teng21	1 (amyloidogenic), 0 (non-amyloidogenic)
Sequence	SEQ_CAPSID	7935	3364680	3864	4071	VIRALpro	Prediction of capdsid proteins	Galiez16	1 (capsid protein), 0 (non-capsid protein)
Sequence	SEQ_DISULFIDE	2547	614470	897	1650	Dipro	Prediction of disulfide bridges in sequences	Cheng06	1 (sequence with SS bond), 0 (sequence without SS bond)
Sequence	SEQ_LOCATION	1835	732398	1045	790	nan	Prediction of subcellular location of protein (cytoplasm vs plasma membrane)	Shen19	1 (protein in cytoplasm), 0 (protein in plasma membrane)
Sequence	SEQ_SOLUBLE	17408	4432269	8704	8704	SOLpro	Prediction of soluble and insoluble proteins	Magnan09	1 (soluble), 0 (insoluble)
Sequence	SEQ_TAIL	6668	2671690	2574	4094	VIRALpro	Prediction of tail proteins	Galiez16	1 (tail protein), 0 (non-tail protein)
Domain	DOM_GSEC	126	92964	63	63	nan	Prediction of gamma-secretase substrates	Breimann25a	1 (substrate), 0 (non-substrate)
Domain	DOM_GSEC_PU	694	494524	63	0	nan	Prediction of gamma-secretase substrates (PU dataset)	Breimann25a	1 (substrate), 2 (unknown substrate status)

Amino Acid Scale Datasets

Various amino acid scale datasets are provided.

Dataset	Description	# Scales	Reference
scales	Amino acid scales (min-max normalized)	586	Breimann24b
scales_raw	Amino acid scales (raw values)	586	Kawashima08
scales_cat	Classification of scales (AAontology)	586	Breimann24b
scales_pc	Principal component (PC) compressed scales	20	Breimann24a
top60	Top 60 scale subsets (AAclust)	60	Breimann24a
top60_eval	Evaluation of top 60 scale subsets	60	Breimann24a

AAontology

AAontology ([Breimann24b]) provides a two-tiered system for amino acid classification, designed to enhance the interpretability of sequence-based protein predictions. It encompasses 586 physicochemical scales, which are systematically arranged into 67 subcategories and further grouped into 8 categories. Every scale, subcategory, and main category is clearly defined and supported by key references. The scales were grouped into their respective subcategories using a combination of AAclust ([Breimann24a]) clustering and assessments of biological similarity. Those scales that couldn’t be allocated to a specific subcategory are labeled as ‘unclassified’.

Categories

Category	Category Description	Key References	# Scales	# Unclassified Scales	# Subcategories	# Subcategories (n>=4 Scales)	# Subcategories (n<4 Scales)
ASA/Volume	Subcategories regarding volume or preference of residues being accessible (e.g., solvent accessible surface area (ASA)) or buried)	Chothia, 1976; Lins et al., 2003	64	0	5	4	1
Composition	Frequency of occurrence in proteins (average) or in proteins with distinct cellular localization (e.g., membrane proteins or mitochondria proteins)	Nakashima et al., 1990; Nakashima-Nishikawa, 1992	58	2	5	5	0
Conformation	Frequency of occurrence in distinct structural conformation (e.g., α-helix, extended conformations such as β-sheet or β-strand, ranodm coil, or β-turn)	Tanaka-Scheraga, 1977; Chou-Fasman, 1978b; Richardson-Richardson, 1988; Qian-Sejnowski, 1988; Aurora-Rose, 1998	224	19	24	20	4
Energy	Various subcategories regarding the term of “energy” (e.g., charge, entropy, free energy, or non-bonded energy)	Charton-Charton, 1983; Guy, 1985; Radzicka-Wolfenden, 1988	36	5	9	3	6
Others	Subcategories that could not be assigned to the other categories (e.g., principal component analysis, mutability)	Sneath, 1966	17	5	6	0	6
Polarity	Subcategories regarding hydrophobicity, hydrophilicity, or amphiphilicity	Kyte-Doolittle, 1982; Mitaku et al., 2002; Koehler et al., 2009	111	6	6	5	1
Shape	Subcategories regarding shape and steric characteristics of residues (e.g., side chain angle, symmetry, or measures of graph-based representation of residues such as eccentricity)	Prabhakaran-Ponnuswamy, 1982; Kakraba-Knisley, 2016	45	4	6	4	2
Structure-Activity	Subcategories regarding flexibility, stability, or backbone dynamics	Vihinen et al., 1994; Bastolla et al., 2005	31	1	6	3	3

Subcategories

Category	Subcategory	# Scales	Subcategory Description	Key References
ASA/Volume	Accessible surface area (ASA)	23	Solvent accessible surface area (ASA) in folded proteins (Lins), measuring a residues surface area that is accessible/exposed to solvent (typically water) at the protein surface	Lins et al., 2003; Chothia, 1976
ASA/Volume	Buried	12	Tendency of residue being buried in folded proteins (Janin), as opposed to being accessible at the protein surface (Chothia)	Janin et al., 1978; Chothia, 1976
ASA/Volume	Hydrophobic ASA	3	Hydrophobic solvent accessible surface area (ASA) in folded proteins (Lins), measuring a residues surface area that is hydrophobic and exposed to solvent (typically water) at the protein surface	Lins et al., 2003
ASA/Volume	Partial specific volume	9	Effective volume in water, accounting for physical volume and any extra water displacement caused by residue-solvent interactions (mainly hydrophobic ones)	Bull-Breese, 1974
ASA/Volume	Volume	17	Volume or size of residue	Bigelow, 1967
Composition	AA composition	23	Frequency of occurrence in proteins (Jones), denoted as amino acid (AA) composition by Dayhoff	Dayhoff, 1978b; Jones et al., 1992
Composition	AA composition (surface)	5	Frequency of occurrence at protein surface, as opposed to occurrence at protein interior (compared with “AA composition”, lower for unpolar amino acids)	Fukuchi-Nishikawa, 2001
Composition	Membrane proteins (MPs)	13	Frequency of occurrence in membrane proteins (MPs)	Nakashima et al., 1990; Cedano et al., 1997
Composition	Mitochondrial proteins	4	Frequency of occurrence in mitochondrial proteins (similar to membrane proteins, but with less Val)	Nakashima et al., 1990
Composition	MPs (anchor)	11	Frequency of occurrence in N-/C-terminal anchoring region of membrane proteins (cf. high N-terminal and C-terminal helix capping propensity (Asp, Glu resp. Lys, Arg) observed by Aurora-Rose). Characterized by a high partition energy (Guy, 1985)	Punta and Maritan, 2003; Aurora-Rose, 1998; Guy, 1985
Composition	Unclassified (Composition)	2	nan	nan
Conformation	Coil	13	Frequency of occurrence in random coil (see window positions given by Qian-Sejnowski)	Robson-Suzuki, 1976; Qian-Sejnowski, 1988
Conformation	Coil (C-term)	4	Frequency of occurrence at C-terminus in random coil (see window positions in Qian-Sejnowski)	Qian-Sejnowski, 1988
Conformation	Coil (N-term)	3	Frequency of occurrence at N-terminus in random coil (see window positions in Qian-Sejnowski)	Qian-Sejnowski, 1988
Conformation	Linker (>14 AA)	6	Frequency of occurrence in linker (length>14 residues)	George-Heringa, 2003
Conformation	Linker (6-14 AA)	6	Frequency of occurrence in medium sized linker (length between 6 to 14 residues)	George-Heringa, 2004
Conformation	Unclassified (Conformation)	19	nan	nan
Conformation	α-helix	36	Frequency of occurrence in right-handed α-helix, defined as helical structure with 3.6 residues per turn	Chou-Fasman, 1978b
Conformation	α-helix (C-cap)	4	Frequency of occurrence at C-cap position, defined as C-terminal interface residue, which is half in and half out of the helix (Richardson-Richardson); denoted as helix termination parameter (Finkelstein et al.)	Richardson-Richardson 1988; Aurora-Rose, 1998, Finkelstein et al., 1991
Conformation	α-helix (C-term, out)	5	Frequency of occurrence at C-terminus outside of right-handed α-helix, i.e., after end of helix, denoted as C-cap (Aurora-Rose) for C-terminal helix capping (Richardson-Richardson)	Richardson-Richardson 1988; Aurora-Rose, 1997
Conformation	α-helix (C-term)	8	Frequency of occurrence at C-terminus inside right-handed α-helix, i.e., before end of helix, denoted as C-cap (Aurora-Rose) for C-terminal helix capping (Richardson-Richardson)	Chou-Fasman, 1978b; Richardson-Richardson 1988; Aurora-Rose, 1998
Conformation	α-helix (left-handed)	11	Frequency of occurrence in left-handed α-helix	Tanaka-Scheraga, 1977
Conformation	α-helix (N-cap)	5	Frequency of occurrence at N-cap position, defined as N-terminal interface residue, which is half in and half out of the helix (Richardson-Richardson); denoted as helix initiation parameter (Finkelstein et al.)	Richardson-Richardson 1988; Aurora-Rose, 1998, Finkelstein et al., 1991
Conformation	α-helix (N-term, out)	3	Frequency of occurrence at N-terminus outside of right-handed α-helix, i.e., before start of helix, denoted as N-cap (Aurora-Rose) for N-terminal helix capping (Richardson-Richardson)	Richardson-Richardson 1988; Aurora-Rose, 1998
Conformation	α-helix (N-term)	7	Frequency of occurrence at N-terminus inside right-handed α-helix, i.e., after start of helix, denoted as N-cap (Aurora-Rose) for N-terminal helix capping (Richardson-Richardson)	Chou-Fasman, 1978b; Richardson-Richardson 1988; Aurora-Rose, 1998
Conformation	α-helix (α-proteins)	5	Frequency of occurrence in α-helix (based on only α-helical structures)	Geisow-Roberts, 1980
Conformation	β/α-bridge	2	Frequency of occurrence in the ‘β/α-bridge’ region of Ramachandran plot, reflecting conformational state between β-sheet (top-left quadrant) and right-handed α-helix (bottom-left quadrant)	Tanaka-Scheraga, 1977; Pauling et al., 1951
Conformation	β-sheet	21	Frequency of occurrence in β-sheet (see window positions in Qian-Sejnowski)	Chou-Fasman, 1978b; Qian-Sejnowski, 1988
Conformation	β-sheet (C-term)	5	Frequency of occurrence at C-terminus in β-sheet (see window positions in Qian-Sejnowski)	Qian-Sejnowski, 1988
Conformation	β-sheet (N-term)	5	Frequency of occurrence at N-terminus in β-sheet (see window positions in Qian-Sejnowski)	Qian-Sejnowski, 1988
Conformation	β-strand	15	Frequency of occurrence extended chain conformation/β-strand (typically 6-10 residues long, n>=2 parallel or antiparallel β-strands form a β-sheet)	Chou-Fasman, 1978; Lifson-Sander, 1979
Conformation	β-turn	21	Frequency of occurrence in β-turn (also called e.g. β-bend, reverse turn, tight turn), consisting of 4 consecutive residues forming a 180° back folded chain (Chou-Fasman), where two end residues (i -> i+3) form a main chain hydrogen bond	Chou-Fasman, 1978b, Robson-Suzuki, 1976
Conformation	β-turn (C-term)	6	Frequency of occurrence at 3rd or 4th position in β-turn (3rd position is denoted as chain reversal state S by Tanaka-Scheraga)	Chou-Fasman, 1978b; Tanaka-Scheraga, 1977
Conformation	β-turn (N-term)	6	Frequency of occurrence at 1st or 2nd position in β-turn (2nd position is denoted as chain reversal state R by Tanaka-Scheraga)	Chou-Fasman, 1978b; Tanaka-Scheraga, 1977
Conformation	β-turn (TM helix)	3	Frequency of occurrence in β-turn when placed in middle of transmembrane (TM) helix	Monné et al., 1999
Conformation	π-helix	5	Frequency of occurrence in right-handed π-helix, defined as helical structure with 4.4 residues per turn (compared with “α-helix”, lower for Ala, Asp, Glu, and Gln)	Fodje-Al-Karadaghi, 2002
Energy	Charge	2	Net charge and donor charge capability. Net charge is defined as 1 for positively charged residues (Arg, Lys), 0 for negatively charged residues (Asp, Glu), and 0.5 otherwise. Donor charge capability is defined as presence (1) or absence (0) of charge transfer donor capability in residue.	Klein et al., 1984; Charton-Charton, 1983
Energy	Charge (negative)	2	Negative charge and transfer charge. Negative charge is defined as presence (1) or absence (0) of negative charge in residue (Asp, Glu).Transfer charge is defined as presence (1) or absence (0) of charge transfer acceptor capability in residue.	Fauchere et al., 1988; Charton-Charton, 1983
Energy	Charge (positive)	1	Presence (1) or absence (0) of positive charge in residue (Arg, Lys, His)	Fauchere et al., 1988
Energy	Electron-ion interaction pot.	3	Electron-ion interaction potential, defined as the average energy state in a residue of all valence electrons (i.e., electrons that can participate in chemical bond formation)	Cosic, 1994
Energy	Entropy	3	Conformational entropy, associated with the number of possible conformations a residue can participate in (e.g., Ala has a low entropy due to is strong α-helix formation)	Hutchens, 1970
Energy	Free energy (unfolding)	8	Activation Gibbs free energy of unfolding in water or denaturant; measure of conformational stability	Yutani et al., 1987; Radzicka-Wolfenden, 1988
Energy	Free energy (folding)	5	Free energy of formation of α-helix or extended structure; measure of conformational instability of α-helix resp. extended structure (highest value for structure breaking Pro)	Munoz-Serrano, 1994
Energy	Isoelectric point	3	pH at which residue is electrically neutral	Zimmerman et al., 1968
Energy	Non-bonded energy	4	Average non-bonded energy E per residue in 16 protein crystal structures, where E is computed as sum of pairwise interactions between constituent atoms (using Lennard-Jones potential)	Oobatake-Ooi, 1977
Energy	Unclassified (Energy)	5	nan	nan
Others	Mutability	3	Relative mutability of a residue, defined as the number of observed changes of a residue divided by it´s frequency of occurrence	Jones et al., 1992
Others	PC 1	1	Vector of Principal Component analysis performed by Sneath, described as ‘aliphaticity’ (i.e., presence of linear, non-aromatic carbon chains)	Sneath, 1966
Others	PC 2	2	Vector of Principal Component analysis performed by Sneath, described as ‘hydrogenation’ (approximately corresponds to the inverse of the number of reactive groups in a residue)	Sneath, 1966
Others	PC 3	2	Vector of Principal Component analysis performed by Sneath, described as ‘aromaticity’ (i.e., aromatic property of residues)	Sneath, 1966
Others	PC 4	2	Vector of Principal Component analysis performed by Sneath, described as ‘hydroxythiolation’ (might reflect hydrogen bonding potential)	Sneath, 1966
Others	PC 5	2	Vector of Principal Component analysis performed by Wold	Wold et al., 1987
Others	Unclassified (Others)	5	nan	nan
Polarity	Amphiphilicity	6	Preference of residue to occur at interface of polar and non-polar solvents (esp., membrane-water interface)	Mitaku et al., 2002
Polarity	Amphiphilicity (α-helix)	13	Characteristic of residue to form amphipathic α-helices (compared to “Amphiphilicity”, higher for unpolar amino acids), highly correlating with signal sequence helical potential (Argos et al., 1982)	Cornette et al., 1987; Argos et al., 1982
Polarity	Hydrophobicity	38	Preference of residue for non-polar/hydrophobic environment, measured as transfer free energy from non-polar solvent to water or from inside of a protein to surface/outside	Kyte-Doolittle, 1982; Eisenberg-McLachlan 1986
Polarity	Hydrophobicity (interface)	3	Preference of residue for non-polar/hydrophobic environment at membrane interfaces	Koehler et al., 2009
Polarity	Hydrophobicity (surrounding)	17	Total hydrophobicity of residues appearing within an 8 Angstrom radius volume, describing the internal packing arrangements of residues in globular proteins	Ponnuswamy et al., 1980; Wolfenden et al., 1981
Polarity	Hydrophilicity	28	Preference of residue for polar/hydrophilic environment, measured as transfer free energy from water to non-polar solvent	Kyte-Doolittle, 1982; Radzicka-Wolfenden, 1988
Polarity	Unclassified (Polarity)	6	nan	nan
Shape	Graph (1. eigenvalue)	5	Measure of graph-theoretic representation of residue, defined as eigenvalue of Laplacian matrix of undirected node-weighted graph (nodes represent atoms (weighted by mass) and edges represent molecular bonds)	Kakraba-Knisley, 2016
Shape	Graph (2. eigenvalue)	3	Measure of graph-theoretic representation of residue, defined as second smallest eigenvalue of Laplacian matrix of undirected node-weighted graph (nodes represent atoms (weighted by mass) and edges represent molecular bonds)	Kakraba-Knisley, 2016
Shape	Side chain length	19	Length of side chain and graph-based size measures like eccentricity of undirected node-weighted graph (nodes represent atoms (weighted by mass) and edges represent molecular bonds)	Charton-Charton, 1983; Kakraba-Knisley, 2016
Shape	Reduced distance	5	Reduced distance from the center of mass of a protein, defined as actual distance divided by the root-mean-square radius of gyration of the radius (e.g., reduced distance > 1 means that residue is farther away from center of mass than the average)	Rackovsky-Scheraga, 1977
Shape	Shape and Surface	3	Measure of relationships between the physical form of an amino acid and its solvent accessibility (e.g., rate at which the accessible surface increases relative to the distance from the protein center)	Prabhakaran-Ponnuswamy, 1982
Shape	Steric parameter	6	Measure of the steric factors of a residue such as branching, it´s symmetry, or side chain angles	Fauchere et al., 1988
Shape	Unclassified (Shape)	4	nan	nan
Structure-Activity	Backbone-dynamics (-CH)	3	α-CH chemical shifts of residue as measure of general backbone-dynamics/stability	Bundi-Wuthrich, 1979
Structure-Activity	Backbone-dynamics (-NH)	2	α-NH chemical shifts of residue as measure of general backbone-dynamics/stability	Bundi-Wuthrich, 1979
Structure-Activity	Flexibility	11	Flexibility parameter, measured as average B-factor (atomic temperature factor obtained from protein crystal structures)	Vihinen et al., 1994
Structure-Activity	Flexibility (2 rigid neighbors)	3	Flexibility parameter, measured as B-factor for residue being surrounded by two rigid neighbors (compared with “Flexibility”, lower for Gly and Ser)	Vihinen et al., 1994
Structure-Activity	Stability	7	Contribution of residue to protein stability (particularly depending on hydrophobic interactions)	Ptitsyn-Finkelstein, 1983; Zhou-Zhou, 2004; Bastolla, 2005
Structure-Activity	Stability (helix-coil)	4	Contribution of residue to protein stability for helix-coil equilibrium	Ptitsyn-Finkelstein, 1983; Sueki et al., 1984
Structure-Activity	Unclassified (Structure-Activity)	1	nan	nan