A linguistic model for the rational design of antimicrobial peptides

Abstract

Antimicrobial peptides (AmPs) are small proteins that are used by the innate immune system to combat bacterial infection in multicellular eukaryotes. There is mounting evidence that these peptides are less susceptible to bacterial resistance than traditional antibiotics and could form the basis for a new class of therapeutic agents. Here we report the rational design of new AmPs that show limited homology to naturally occurring proteins but have strong bacteriostatic activity against several species of bacteria, including Staphylococcus aureus and Bacillus anthracis. These peptides were designed using a linguistic model of natural AmPs: we treated the amino-acid sequences of natural AmPs as a formal language and built a set of regular grammars to describe this language. We used this set of grammars to create new, unnatural AmP sequences. Our peptides conform to the formal syntax of natural antimicrobial peptides but populate a previously unexplored region of protein sequence space.

Prediction and Rational Design of Antimicrobial Peptides

“…Some years later, Loose et al (2006) developed a similar but more sophisticated de novo method, the linguistic model. According to this model, AMPs seem to be a formal language with grammar composed of several rules (patterns) and a vocabulary (amino acids).…”

An SVM Model Based on Physicochemical Properties to Predict Antimicrobial Activity from Protein Sequences with Cysteine Knot Motifs

“…AMPs are a very diverse and abundant group, being divided in several classes, but some of them share some physicochemical characteristics, some studies propose that they are non essential, but the determinant for activity is the tertiary structure [4], however, other studies show that the physicochemical characteristics modulate the antimicrobial activity [5]. Some classes of AMP have a special structural feature, a cysteine knot motif with three disulfide linkages in their structures, which provides a major stability to the structure.…”

Designing biomimetic antifouling surfaces

“…Bioinspired AF coatings might not just come from looking at the external environment. Loose et al (2006) report borrowing aspects from the human innate immune system by exploring the incorporation of small antimicrobial peptides into surfaces. In a similar vein, aspects of mucosal immunity, which is important in preventing bacteria sticking to human epithelial cells, might be exploited for large engineered systems.…”