Laboratorio Virtual NANOCOSMOS, Departamento de Medio Ambiente y Energía, Centro de Investigación en Materiales Avanzados, Chihuahua 31136, Mexico.
Departament de Química, Facultat de Ciènces, Universitat de les Illes Balears, E-07122 Palma de Mallorca, Spain.
Mar Drugs. 2022 Jan 24;20(2):97. doi: 10.3390/md20020097.
As a continuation of our research on the chemical reactivity, pharmacokinetics and ADMET properties of cyclopeptides of marine origin with potential therapeutic abilities, in this work our already presented integrated molecular modeling protocol has been used for the study of the chemical reactivity and bioactivity properties of the Veraguamides A-G family of marine natural drugs. This protocol results from the estimation of the conceptual density functional theory (CDFT) chemical reactivity descriptors together with several chemoinformatics tools commonly considered within the process of development of new therapeutic drugs. CP-CDFT is a branch of computational chemistry and molecular modeling dedicated to the study of peptides, and it is a protocol that allows the estimation with great accuracy of the CDFT-based reactivity descriptors and the associated physical and chemical properties, which can aid in determining the ability of the studied peptides to behave as potential useful drugs. Moreover, the superiority of the MN12SX density functional over other long-range corrected density functionals for the prediction of chemical and physical properties in the presence of water as the solvent is clearly demonstrated. The research was supplemented with an investigation of the bioactivity of the molecular systems and their ADMET (absorption, distribution, metabolism, excretion, and toxicity) parameters, as is customary in medicinal chemistry. Some instances of the CDFT-based chemical reactivity descriptors' capacity to predict the pKas of peptides as well as their potential as AGE inhibitors are also shown.
作为我们对具有潜在治疗能力的海洋源环肽的化学反应性、药代动力学和 ADMET 性质研究的延续，在这项工作中，我们已经提出的综合分子建模方案已用于研究海洋天然药物 Veraguamides A-G 家族的化学反应性和生物活性性质。该方案源自概念密度泛函理论 (CDFT) 化学反应性描述符的估计，以及在开发新治疗药物过程中通常考虑的几种化学信息学工具。CP-CDFT 是计算化学和分子建模的一个分支，专门研究肽，它是一个允许非常准确地估计基于 CDFT 的反应性描述符以及相关物理和化学性质的方案，这有助于确定研究肽作为潜在有用药物的能力。此外，MN12SX 密度泛函在预测存在水作为溶剂时的化学和物理性质方面优于其他长程校正密度泛函，这一点得到了清楚的证明。该研究还补充了对分子系统的生物活性及其 ADMET（吸收、分布、代谢、排泄和毒性）参数的研究，这在药物化学中是很常见的。还展示了基于 CDFT 的化学反应性描述符预测肽的 pKas 以及它们作为 AGE 抑制剂的潜力的一些实例。
