Toward computer-made artificial antibiotics

[Display omitted] •Computational tools for the guided design of novel antibiotics.•The importance of biological descriptors and computational biology for the development of enhanced drugs.•Peptide-based molecules represent promising approach to combat multidrug-resistant microorganisms. Merging concepts from synthetic biology and computational biology may yield antibiotics that are less likely to elicit resistance than existing drugs and that yet can fight drug-resistant infections. Indeed, computer-guided strategies coupled with massively parallel high-throughput experimental methods represent a new paradigm for antibiotic discovery. Infections caused by multidrug-resistant microorganisms are increasingly deadly. In the current post-antibiotic era, many of these infections cannot be treated with our existing antimicrobial arsenal. Furthermore, we may have already exhausted the category of large molecules produced in nature having antimicrobial activity: the antibiotic scaffolds we have discovered so far may represent the majority of those that exist. The rise in drug-resistant bacteria and lack of new antibiotic classes clearly call for out-of-the-box strategies. Recent advances in computational synthetic biology have enabled the development of antimicrobials. New molecular descriptors and genetic and pattern recognition algorithms are powerful tools that bring us a step closer to developing efficient antibiotics. We review several computational tools for drug design and a number of recently generated antibiotic candidates, with an emphasis on peptide-based molecules. Design strategies can generate a diversity of synthetic antimicrobial peptides, which may help to mitigate the spread of resistance and combat multidrug-resistant microorganisms.