We describe our efforts to develop an efficient computational algorithm that searches for peptides that bind strongly and selectively to specific biomolecular targets, and to use that algorithm in the design of peptide-based detectors sensors, and drugs. The algorithm, PepBD, is an iterative procedure that involves as many as 100,000 sequence mutation moves and/or peptide backbone conformation moves to arrive at the peptide sequence and conformation that has the lowest binding energy to the target. The top scoring peptides are then further evaluated by performing explicit-solvent atomistic simulations of the peptide–target complex to determine their binding free energies. We describe the application of this method to two projects.
