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.

Combined MD + MC + AABFE approach to design and screening of high-affinity binders to resistin

中文翻译：

---

在计算机上设计肽作为抵抗素的潜在配体。

抵抗素是一种具有生物学意义的激素，因为它与全球关注的几种疾病有关。这项工作旨在设计一系列环状肽作为“先导化合物”，以识别抵抗素的潜在配体。为此，我们提出了一种基于肽设计算法加上两步选择的方法，该选择考虑了选择性，这是配体设计中最被遗忘的步骤之一。按照这种方法，我们已经能够鉴定出几种肽作为设计生物识别元件的强力候选者。这些肽表现出与白蛋白的低得分结合能，良好的水溶性，在300 K下在水中的稳定性以及与抵抗素的高得分结合能。在那些肽中，选择了两个，基于“炼金术绝对结合自由能”方法执行更严格的结合自由能计算。我们能够为开发抗性配体设计的强大候选化合物建立方法论途径。

结合MD + MC + AABFE方法来设计和筛选高亲和力的抵抗素结合剂