Design of Novel Antimicrobial Peptides in a Multi-Stage In Silico Approach

Abstract

One of the main concerns in world public health is the increase in antimicrobial resistance. An important cause is bacteria developing resistance against naturally occurring antimicrobial peptides (AMPs), which are host defensive peptides with high selectivity of interaction with bacterial cells over mammalian cells. Here, we used an in silico design strategy that can be divided in three main stages. In the first stage we used molecular docking simulations of specifically selected peptides from PepBank peptide database to bacterial and mammalian membrane models (one simple and one complex membrane for each), in order to reduce the large amount of available peptides. Second, we used molecular dynamics simulations to propose a list of potential candidates, whose affinities to (the same) bacterial and mammalian membrane models were calculated in the third stage. The combination of these three methods has proven to be an efficient and relatively fast in silico approach that can be used to design new AMP peptides. A reasonable number of potentially effective novel AMP candidates will then be further tested and validated using experimental techniques. Such an approach has the advantage of using available peptide databases to design novel AMPs with significantly lower cost of research. Acknowledgements: This work was supported by a grant of Ministery of Research and Innovation, CNCS - UEFISCDI, project number PN-III-P1-1.1-TE-2016-0032 within PNCDI III, contract no. 99/2018. Keywords: antimicrobial peptides, membrane models, molecular docking, molecular dynamics, peptide affinity.