APD3: the antimicrobial peptide database as a tool for research and education
APD3: the antimicrobial peptide database as a tool for research and education
Guangshun Wang 0
Xia Li 0
Zhe Wang 0
0 Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center , Omaha, NE 68198-6495 , USA
The antimicrobial peptide database (APD, http://aps. unmc.edu/AP/) is an original database initially online in 2003. The APD2 (2009 version) has been regularly updated and further expanded into the APD3. This database currently focuses on natural antimicrobial peptides (AMPs) with defined sequence and activity. It includes a total of 2619 AMPs with 261 bacteriocins from bacteria, 4 AMPs from archaea, 7 from protists, 13 from fungi, 321 from plants and 1972 animal host defense peptides. The APD3 contains 2169 antibacterial, 172 antiviral, 105 anti-HIV, 959 antifungal, 80 antiparasitic and 185 anticancer peptides. Newly annotated are AMPs with antibiofilm, antimalarial, anti-protist, insecticidal, spermicidal, chemotactic, wound healing, antioxidant and protease inhibiting properties. We also describe other searchable annotations, including target pathogens, molecule-binding partners, post-translational modifications and animal models. Amino acid profiles or signatures of natural AMPs are important for peptide classification, prediction and design. Finally, we summarize various database applications in research and education.
INTRODUCTION
Antimicrobial peptides (AMPs) are host defense molecules
universal in the innate immune systems of both
invertebrates and vertebrates. Because these ancient molecules
remain potent after millions of years, they are regarded as
important templates for developing a new generation of
antimicrobials to combat antibiotic resistant superbugs,
HIV1 and cancer (
1–9
). A clear growth of AMP research started
in the 1980s owing to the discoveries of insect cecropins
by Hans Boman, human -defensins by Robert Lehrer and
magainins by Michael Zasloff (
10–12
). It is now accepted
that the functional roles of AMPs are not limited to
antimicrobial. Natural AMPs can have other functions such as
apoptosis, wound healing and immune modulation. In
addition, a balanced expression of AMPs is so important that
either under or over-expression is related to human diseases
(
3–5
).
With the increase of such peptides annually, it was
realized in the 1990s that a database would be useful to help
manage the basic information for AMPs. To our knowledge,
Alex Tossi et al. built the first such database for plant and
animal AMPs in 1998 (
13
). Unfortunately, this resource is
no longer accessible online. In 2004, both the APD and
ANTIMIC were published. In 2012, ANTIMIC with 1700
entries (
14
) was replaced by DAMPD with a reduced
number of 1232 entries (
15
). The 2004 version of the
antimicrobial peptide database (APD) with 525 AMPs (
16
) was
widely accepted and utilized. In 2009, it was updated to
the APD2 with 1228 entries (
17
). Since the publication of
the APD2, the database web hits increased exponentially
(over 1 million in 2014). One of the most important
reasons for this could be that the APD registers AMPs with
a set of defined criteria and is regularly updated by an
investigator in the AMP field. Furthermore, new features are
added to the database continuously. In addition, each
entry is highly integrated with additional peptide information
covering various aspects of AMPs. This original database
inspired the construction of more recent databases (
18–27
).
To help users better use this resource, here we summarize
the main features of this updated database, which we refer
to as the APD3. We also highlight multiple applications of
this database in both research and education.
DATABASE MAIN FEATURES
To generate a clean data set, the APD3 has set up criteria
for peptide registration. This database currently focuses on
(i) natural AMPs with (ii) a known amino acid sequence,
(iii) biological activity and (iv) a size less than 100 residues.
More recently, the polypeptide size was further relaxed to
200 residues so that important human antimicrobial
proteins can be included. A unique and powerful feature of the
APD3 is that its search interface consists of a pipeline of
search functions. The more one selects or enters, the less
one will get. Without activating anything in the interface,
a simple search returns all the peptides in the database
(curD1088 Nucleic Acids Research, 2016, Vol. 44, Database issue
rent total 2619). The users can filter the information freely
at their will. To make it more convenient, the APD3 has
enhanced the search interface by re-grouping the existing
search icons into functional zones based on information
types and by adding new search icons for peptide activity. At
the bottom of the search page, users can sort the
information based on peptide APD ID (default), net charge, length
and hydrophobic content. In the following, we briefly
describe the main features of the current APD3, ranging from
p (...truncated)