Abstract: Cyclic peptides (CPs) are highly sought after for several unique applications. For example, CPs can target protein surfaces with high affinity and selectivity, thereby inhibiting specific protein–protein interactions that cannot be easily targeted with other molecules. New inhibitors will enable mechanistic studies to dissect the functions of individual protein–protein interactions in the complicated cellular interactome. However, robust application of this fundamentally interesting class of molecules for these and other purposes is limited by our poor capacity to predict CP structures and the resulting inability to rationally design functional CPs. In this talk, we describe an efficient enhanced sampling method to simulate CPs, using which we aim to fill the knowledge gap of CP sequence–structure relationships, and enable rational design of CPs with desired structures.