Departamento de Física Aplicada, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Mérida, Apartado Postal 73 "Cordemex", 97310, Mérida, Mexico.
J Mol Model. 2020 Apr 15;26(5):101. doi: 10.1007/s00894-020-4338-3.
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.
抵抗素是一种具有生物学意义的激素，因为它与几种全球性关注的疾病有关。本工作旨在设计一系列环状肽作为“先导化合物”，以鉴定抵抗素的潜在配体。为此，我们提出了一种基于肽设计算法和两级选择的方法，该方法考虑了配体设计中最容易被忽视的步骤之一的选择性。按照这种方法，我们已经能够确定几种肽作为生物识别元件设计的有力候选者。这些肽与白蛋白的结合能得分较低，水溶性好，在 300 K 下在水中稳定，与抵抗素的结合能得分较高。在这些肽中，选择了两种，以基于变分绝对结合自由能方法进行更严格的结合自由能计算。我们能够为抵抗素配体设计建立一种强有力的候选方法。
