In silico design of peptides as potential ligands to resistin

Resistin is a hormone of biological interest due to its connection with several diseases of worldwide concern. This work aims to design a series of cyclic peptides as "lead compounds" to identify potential ligands to resistin. To this end, we propose an approach based on a peptide design algorithm plus a two-stage selection which accounts for selectivity, one of the most forgotten steps in the design of ligands. Following this approach, we have been able to identify several peptides as strong candidates for the design of elements of bio-recognition. Those peptides present low scoring binding energy to albumin, good water solubility, stability in water at 300 K, and high scoring binding energy to resistin. Among those peptides, two were chosen, to perform a more rigorous calculation of binding free energy based on the Alchemical Absolute Binding Free Energy method. We were able to establish a methodological route for the development of strong candidates for the design of ligands to resistin. Graphical Abstract Combined MD + MC + AABFE approach to design and screening of high-affinity binders to resistin.