Rational, Computer-Enabled Peptide Drug Design: Principles, Methods, Applications and Future Directions
Peptides provide promising templates for developing drugs to occupy a middle space between small molecules and antibodies and for targeting 'undruggable' intracellular protein-protein interactions. Importantly, rational or in cerebro design, especially when coupled with validated in silico tools, can be used to efficiently explore chemical space and identify islands of 'drug-like' peptides to satisfy diverse drug discovery program objectives. Here, we consider the underlying principles of and recent advances in rational, computer-enabled peptide drug design. In particular, we consider the impact of basic physicochemical properties, potency and ADME/Tox opportunities and challenges, and recently developed computational tools for enabling rational peptide drug design. Key principles and practices are spotlighted by recent case studies. We close with a hypothetical future case study.
Diller D, Swanson J, Bayden A, Audie J. Rational, computer-enabled peptide drug design: principles, methods, applications and future directions. Future Med. Chem. 7(16), 2173-2193 (2015)