The Importance of Amino Acid Composition in Natural AMPs: An Evolutional, Structural, and Functional Perspective

components of natural host defense systems against infectious pathogens (Zasloff, 2002; Boman, 2003; Hancock and Sahl, 2006). They are ubiquitous in nature and have been found in nearly all forms of life, ranging from single-celled bacteria to multicellular organisms such as plants and animals. AMPs are short peptides (5–100 amino acids) with an average net charge of +3 (Wang, 2010). They can display broad or narrow-spectrum antimicrobial activities. The fact that AMPs are effective against multidrug resistance pathogens, including suppression of biofilm formation, deserves our attention (Menousek et al., 2012). In addition to direct bacterial elimination, these peptides have regulatory effects on immune systems. Consequently, AMPs are also referred to as host defense peptides (Hancock and Sahl, 2006). To decode the key elements behind the functional diversity of AMPs, we have been taking time and efforts in constructing a comprehensive database that annotates such information. The first version of the Antimicrobial Peptide Database (APD; http://aps.unmc.edu/AP/ main.html) was established in 2003 (Wang and Wang, 2004) and the database has since been further developed (Wang et al., 2009). The APD contained 1973 entries as of May 2012. To facilitate our bioinformatic analysis, we will register a peptide into the APD if it is (1) from natural sources; (2) with minimal inhibitory concentration (MIC) of less than 100 μM or 100 μg/mL; (3) less than 100 amino acid residues; and (4) with a characterized amino acid sequence (Wang, 2010). The APD allows users to extract important parameters (e.g., charge, hydrophobicity, motif, and structure) that determine peptide function. In particular, our database enables the generation of the amino acid composition for a select peptide or a family of AMPs with a common feature. This bioinformatic tool thus uncovers the amino acid use in natural AMPs from different sources, with different functions, or three-dimensional structures. This opinion article highlights the critical roles of the amino acid composition in naturally occurring AMPs in terms of evolutional, structural, and functional significance. Moreover, its application in designing and predicting new AMPs will also be discussed.