Well-Tempered MetaDynamics based method to evaluate universal peptidomimetics

Peptidomimetics are a broad family of compounds designed to mimic the main structural features of peptides, avoiding their metabolic drawbacks. In particular, universal peptidomimetics use only peptide side-chain analogs to mimic different secondary structures. In this work, a novel method is proposed to identify universal peptidomimetics. It is based on a single Meta-Dynamics simulation which allows the reconstruction of the Free Energy Surface of the compound of interest. Subsequently, cluster analysis is carried out to obtain representative structures. Such conformers are then compared to ideal secondary structures to assess their mimicking ability. This protocol was validated against known universal peptidomimetics. (C) 2018 Published by Elsevier B.V.