The Database of Antimicrobial Activity and Structure of Peptides (DBAASP) has been created to provide users with information on detailed chemical structure and activity for those peptides which antimicrobial activity against particular targets have been evaluated experimentally. The database is manually curated and contains information on ribosomal, nonribosomal and synthetic peptides that show antimicrobial activity as Monomers, Multimers and Multi-Peptides.
Ribosomal peptides are peptides which amino acid sequence is genetically encoded and naturally produced despite its termini modification.
Monomer - consists of one polypeptide chain.
Multimer - consists of two or more polypeptide chains with interchain covalent bond(s).
Multi-Peptide - consists of two or more different polypeptide chains in equimolar concentrations without interchain covalent bond.
In Statistics are presented three kinds of data: General Data, Compositional Data, Physicochemical Data.
General Data consists of data on: a) compositions according to type of synthesis, complexity, target groups etc.; b) distribution of lengths.
Compositional Data consists of data on: a) amino acid compositions b) Statistics of occurrence of sequential pairs of residues.
Physicochemical Data consists of data on distributions of values of different phyico-chemical parameters such as hydriphobicity, amphipathicity, isoelectical point etc.
By means of “Property calculation” various physico-chemical characteristics of peptides are calculated, such as hydrophobicity, hydrophobic moment, charge, isoelectric point, etc.
API describes how the database can be accessed with programs. All resources (individual entries as well as sets of entries retrieved by queries) are accessible using simple URLs.
Prediction predicts antimicrobial and hemolytic/cytotoxic activity of a peptide.
Users are provided with information on synonyms (based on the NCBI Taxonomy Database). Information about existence of synonyms of particular target species can be obtained by search tool.
For detailed information see links below:
Page Search includes several options:
Peptides can be found using one (77), several (77, 99) or interval (77-99) of ID.
In this field either full or part of peptide name should be written.
Search by sequence can be performed using two options: 1) Full Sequence and 2) Part of Sequence (peptide can be found by fragment of amino acid chain).
Finds peptides according to the length interval.
N Terminus, C Terminus
Peptides can be found by their termini modification. Modification types are presented in dropdown menu. Description of each type is given below in Abbreviations.
The peptides are divided into three types by complexity - Monomers, Multimers and Multi-Peptides. Complexity type should be selected from dropdown menu.
Unusual Amino Acid
This field gives possibility to find peptides containing unusual, posttranslationally modified or artificial amino acids. Such amino acids are presented in dropdown menu (see abbreviations).
Finds monomers with intrachain covalent bonds. Bond type should be selected from dropdown menu (see abbreviations).
Finds peptides according to synthesis type (ribosomal, nonribosomal and synthetic). Synthesis type should be selected from dropdown menu.
This field gives possibility to select peptides according to the kingdom level of taxonomy of source organism. Kingdom can be selected from dropdown menu.
This field gives possibility to select peptides according to the name of the source organism. Latin name (or part of name) of the peptide source organism should be written.
Selects peptides according to the groups of target species. To select the group move mouse pointer over name of a group and click left key of mouse. To select more than one group keep Ctrl key pressed and select the groups by mouse clicking.
Target Object of Cell
Target Object of Cell is the subcellular structure or molecule that peptide interacts with. Selection can be done as described in Target Group.
Selects peptides according to the target species (bacteria, fungus, virus, cancer). Name or part of name of the target species can be used for searching.
Nonstandard Experimental Conditions
Selects peptides which activities are measured in nonstandard salt or pH conditions.
Hemolytic and Cytotoxic activities
Selects peptides with hemolytic and/or cytotoxic activity.
Selects peptides according to UniProt ID. We distinguish three types of Peptide UniProt IDs and they are named as Peptide ID, Precursor ID, Probable Precursor ID.
1) UniProt ID is defined as “Peptide ID” if amino acid sequence coincides to sequence in UniProt entry.
2) UniProt ID is defined as “Precursor ID” if amino acid sequence corresponds to the part of UniProt entry which is defined as precursor.
3) UniProt ID is defined as “Probable Precursor ID” if amino acid sequence corresponds to the part of UniProt entry which can be considered as precursor.
Selects peptides that contain link to PDB database and/or information about MD model.
This field gives possibility to find peptides being synergistic with other peptides or with antimicrobials(including antibiotics). Antimicrobials are presented in dropdown menu. To get information on synergistic data for the peptide one should use the combination of the ID of peptide and option "All with data on synergy" from drop down menu of "Synergy". The table "Synergy between current peptide and Antimicrobials" in the peptide-card of the query gives information on synergიstic relations between query and other peptides.To get information on synergistic data for antimicrobials, one should choose the name of antimicrobial only.
Each row of the table corresponds to particular peptide. Each row contains information on peptide ID, name, N terminus modification, sequence, C terminus modification. Lowercase letter indicates D amino acid. Posttranslationally modified, unusual or artificial amino acids are depicted by X or x. (Exception is disulfide bond of cysteine where cysteines are depicted by C or c). In order to get full information on peptide one should click on View at the right edge of row.
Ranking Search gives information about peptides and activities for given target species/cell and activity/lysis measure ranked by activity value. Target species/cell and activity measure/lysis can be selected from dropdown menu. Search by target species/cell and activity/lysis measure can be combined with other search options: Sequence Length, N Terminus, C Terminus, Complexity, Unusual Amino Acid, Bond, Synthesis Type, Kingdom, Source, Medium, CFU. For ranking search some activity measures are systematized.
Hemolytic/cytotoxic measures of activity
In literature several measures are used for cytotoxicity and hemolysis. ECn (n=25, 50), HCn (n=10, 50, 100), HDn (n=50), HLn (n=50), LCn (n=50), LDn (n=50) are used as measures of hemolysis. All of them are defined as peptide concentration at which n% erythrocyte lysis occurs. In addition MHC is defined as minimal peptide concentration at which no detectable hemolytic activity is observed. Some authors define MHC as a peptide concentration at which n% hemolysis occurs (n=0–10). Thus, for “Ranking search” it is reasonable to do standardization of the measures and the common term – “n% Hemolysis“ is used instead of various denotations.
EC50 and LC50 are used for cytotoxic measure. They present peptide concentration inducing a 50% cell death. Instead of these two measurements we use 50% Cell death.
Antiviral activity measurements
AMP antiviral activity should be distinguished from antibacterial activity. Bacteria is fully self-sufficient objects and able to grow without host cells. Therefore, bacteria growth inhibition or killing is measured directly. Virus is not self-sufficient object and cannot be reproduced without host cell. Consequently, inhibition of the different processes connected with virus multiplication in the host cell are: activities of integrase; reverse transcriptase; protease; replication; Vif-Vif binding; cell fusion/entry, plaque formation, etc. In literature characteristic measures of these processes are IC50 and EC50. Consequently, systematized is needed.
For ranking search activity measures for integrase activity; reverse transcriptase activity; protease activity and virus replication are systematized as following:
1) Integrase 3' end processing and strand transfer measurements are depicted by IC50 IN 3’EP and IC50 IN ST, respectively.
2) Retroviral reverse transcriptase has three activities: RNA-dependent DNA polymerase, DNA-dependent DNA polymerase and ribonuclease H. For these activities we use IC50 RT RDDP, IC50 RT DDDP and IC50 RT RH, correspondingly.
3) Activity measures for protease activity, replication and plaque formation are denoted by IC50 PR, IC50 REP and IC50 P, respectively.
Measures of Vif-Vif binding; cell fusion/entry etc. cannot be systematized. Therefore, corresponding activities do not take part in ranking search.
As antimicrobial activities were found to differ under various conditions, information on Medium and CFU is given in the Peptide Card.
“Ranking search” provides available information of the antimicrobial activities of the definite target species in the definite medium and with definite CFU.
Prediction section predicts antimicrobial activity of peptides. Web site contains two types of prediction tools: "Prediction of general antibacterial activity" and "Prediction of activity against specific microbial species".
"Prediction of general antibacterial activity" is a tool of prediction of only Linear peptides which are active against some bacterial strain. It based on the machine learning algorithm. Initially the following physico-chemical characteristics of peptides and hydrophobic scales were used: physico-chemical characteristics: Normalized Hydrophobic moment, Normalized Hydrophobicity, Charge Density, Isoelectric Point, Penetration Depth, Orientation of Peptides relative to the surface of membrane (Tilt angle), Propensity to Disordering, Linear Moment, in vitro aggregation (Tango) and in vivo aggregation (Aggrascan); hydrophobic scales: MF - Moon and Fleming scale , KD - Kyte and Doolittle scale , WW - Wimley and White scale , EW - Eisenberg and Weiss scale , UH - Unified Hydrophobicity scale , HW - Hessa and White scale .
Finally, MF hydrophobic scale and the following characteristics were selected: Hydrophobic moment, Charge density and depth-dependent potential (for the detail see ). Peptide should consist of 20 canonical amino acids and sequence be in FASTA format.
"Prediction of activity against specific microbial species" is a tool of prediction of Linear AMPs, which are active against particular strains. Active peptide implies MIC<25 µg/ml. Non-Active peptide implies MIC>100 µg/ml. The strain can be selected from drop-down menu. The number of stains will be permanently risen. Length of the peptide should not exceed 30 amino acids. The server produces one of the two predictive values depending on the prediction: positive predictive value (PPV) for peptides predicted as active and negative predictive value (NPV) for peptides predicted as not active. Taking into account, that for the evaluation activity against Human erythrocytes, non-active peptides are considered as positive, the server gives PPV for peptides not active against Human erythrocytes, and NPV otherwise.
A semi-supervised machine-learning approach relying on density-based clustering algorithm DBSCAN was developed to optimize the predictive model. Moon and Fleming hydrophobic scale and the following characteristics are used in the QSAR study: Normalized Hydrophobic moment, Normalized Hydrophobicity, Charge, Isoelectric Point, Penetration Depth, Orientation of Peptides relative to the surface of membrane (Tilt angle), Propensity to Disordering, Linear Moment and In vitro aggregation .
1. Moon C. P., Fleming K. G. Proc. Natl. Acad. Sci. U. S. A. 2011, 108 (25), 10174-10177.
2. Kyte J., Doolittle R. F. J. Mol. Biol. 1982, 157, 105-132.
3. Wimley W. C., White S. H. Nat. Struct. Biol. 1996, 3, 842-848.
4. Eisenberg D., et al. Proc. Natl. Acad. Sci. U. S. A. 1984, 81, 140-144.
5. Koehler J., et al. Proteins 2009, 76, 13-29.
6. Hessa T., et al. Nature 2005, 433, 377-381.
7. Vishnepolsky B., Pirtskhalava M. J. Chem. Inf. Model. 2014, 54, 1512−1523.
8. Vishnepolsky B., et al. J. Chem. Inf. Model. 2018, 58, 1141-1151.
In this section calculations of the following physiochemical properties can be made: Normalized Hydrophobic Moment, Normalized Hydrophobicity, Net Charge, Isoelectric Point, Penetration Depth, Tilt Angle, Propensity to Disordering, Linear Moment, Propensity to in vitro Aggregation, Angle Subtended by the Hydrophobic Residues, Amphiphilicity Index, Propensity to ppII coil
Normalized Hydrophobic Moment is calculated as hydrophobic moment of the peptide in α-helical approximation by Eisenberg formula (Eisenberg, D. at all, Nature 1982, 299 (5881), 371-374) divided by the peptide sequence length.
Normalized Hydrophobicity is calculated as overall hydrophobicity of the peptide, defined as the sum of transfer (from water into the hydrophobic environment) energy of the residue (hydrophobicity) divided by the peptide sequence length.
Net Charge and Isoelectric Point
were calculated by the method described
Penetration Depth and Tilt Angle are calculated on the base of the peptide energetically most favorable location of the peptide within the membrane bilayer, by the method described in Senes et al., J. Mol. Biol. 2007, 366, 436-448., and Vishnepolsky and Pirtskhalava J. Chem. Inf. Model. 2014, 54, 1512-1523.
Propensity to Disordering is calculated on the base of the balance between hydrophobic and positively charged residues according to Uversky`s formula (Uversky et al., Proteins: Struct. Funct. Gen. 2000, 41 (3), 415-427)
Linear Moment is calculated for estimating the separation of hydrophobic and hydrophilic residues along the peptide chain according to the method, described in Vishnepolsky and Pirtskhalava J. Chem. Inf. Model. 2014, 54, 1512-1523.
Propensity to in vitro Aggregation is calculated based on the TANGO software (Fernandez-Escamilla et al. Nat. Biotechnol. 2004, 22, 1302-1306).
Angle Subtended by the Hydrophobic Residues is calculated on basis of helical wheel representation of the polypeptide chain in the ideal α-helix approximation using in house software. The definition of hydrophobic residues depends on the selected hydrophobic scales (see below).
Amphiphilicity Index is calculated as overall amphiphilicity of the peptide as the sum of the amino acid amphiphilicities, calculated on the base of index database (AAindex) (Kawashima, S. and Kanehisa, M.; Nucleic Acids Res. 28, 374 (2000), Mitaku et al. Bioinformatics., 18, 608-616 (2002)) divided by the peptide sequence length
Propensity to ppII coil is calculated as the sum of the poly-Pro II (ppII) preferences of the comprising amino acids (Adzhubay et al., Biochemical and biophysical research communications, 1987, 146, 934-938) divided by the peptide sequence length. The "ppII coil" is considered as a coil that retains a degree of local order similar to the ppII helix, short stretches of which are interspersed with turns (Tiffany and Krimm, Biopolymers, 1968, 6, 1379-1382).
The following properties Normalized Hydrophobic Moment, Normalized Hydrophobicity, Linear Moment and Angle Subtended by the Hydrophobic Residues can be calculated for different hydrophobic scales, which can be chosen from the drop-down menu. The following hydrophobic scales were used: MF - Moon and Fleming scale (Moon, C. P.; Fleming, Proc. Natl. Acad. Sci. U. S. A. 2011, 108 (25), 10174-10177), KD - Kyte and Doolittle scale (Kyte J., Doolittle R. F. J. Mol. Biol. 1982, 157 (1), 105-132.), WW - Wimley and White scale (Wimley W. C., White S. H. Nat. Struct. Biol. 1996, 3, 842-848.), EW - Eisenberg and Weiss (Eisenberg D. at all Proc. Natl. Acad. Sci. U. S. A. 1984, 81 (1), 140-144.), UH - Unified Hydrophobic scale (Koehler J. at all Proteins 2009, 76, 13-29.) HW - Hessa and White scale (Hessa, T at all Nature 2005, 433, 377-381.)
Values of the properties given in the Peptide Cards have been calculated for the KD scale
Thus, to develop new peptide-based antimicrobial or/and to use combination of AMP with traditional antibiotics, it's valuable to have information on synergy between AMPs and between AMPs and antibiotics respectively. At the moment the attention to synergy is very high. The data on the synergy between different AMPs and antibiotics is growing rapidly. The current version of the database offers data on synergy in the form of the special table in the peptide card of particular peptides for which corresponding data are available. Table presents data on synergy between peptide-card peptide and another peptide or antibiotic/antimicrobial agent. Data includes: susceptibility of the particular strain against the current peptide alone and in combination, susceptibility of the same strain against another peptide/antimicrobial alone and in combination and a values of FICI.
|NCBI Taxonomy database synonyms|