The antimicrobial peptide database provides a platform for decoding the design principles of naturally occurring antimicrobial peptides.

This article is written for the 2020 tool issue of Protein Science. It briefly introduces the widely used antimicrobial peptide database, initially online in 2003. After a description of the main features of each database version and some recent additions, the focus is on the peptide design parameters for each of the four unified classes of natural antimicrobial peptides (AMPs). The amino acid signature in AMPs varies substantially, leading to a variety of structures for functional and mechanistic diversity. Also, Nature is a master of combinatorial chemistry by deploying different amino acids onto the same structural scaffold to tune peptide functions. In addition, the single-domain AMPs may be posttranslationally modified, self-assembled, or combined with other AMPs for function. Elucidation of the design principles of natural AMPs will facilitate future development of novel molecules for various applications.