Mangiatordi Giuseppe Felice, Alberga Domenico, Trisciuzzi Daniela, Lattanzi Gianluca, Nicolotti Orazio
Dipartimento di Farmacia-Scienze del Farmaco, Via Orabona, 4, University of Bari "Aldo Moro", 70126 Bari, Italy.
Institut de Recherche de Chimie Paris CNRS Chimie ParisTech, PSL Research University, 11 rue P. et M. Curie, F-75005 Paris, France.
Int J Mol Sci. 2016 Jul 13;17(7):1119. doi: 10.3390/ijms17071119.
Among the different aquaporins (AQPs), human aquaporin-4 (hAQP4) has attracted the greatest interest in recent years as a new promising therapeutic target. Such a membrane protein is, in fact, involved in a multiple sclerosis-like immunopathology called Neuromyelitis Optica (NMO) and in several disorders resulting from imbalanced water homeostasis such as deafness and cerebral edema. The gap of knowledge in its functioning and dynamics at the atomistic level of detail has hindered the development of rational strategies for designing hAQP4 modulators. The application, lately, of molecular modeling has proved able to fill this gap providing a breeding ground to rationally address compounds targeting hAQP4. In this review, we give an overview of the important advances obtained in this field through the application of Molecular Dynamics (MD) and other complementary modeling techniques. The case studies presented herein are discussed with the aim of providing important clues for computational chemists and biophysicists interested in this field and looking for new challenges.
在不同的水通道蛋白（AQP）中，人类水通道蛋白4（hAQP4）近年来作为一个新的有前景的治疗靶点引起了极大关注。事实上，这种膜蛋白参与了一种名为视神经脊髓炎（NMO）的多发性硬化样免疫病理学过程，以及由水平衡失调导致的多种疾病，如耳聋和脑水肿。在原子水平细节上对其功能和动力学的知识空白阻碍了设计hAQP4调节剂的合理策略的发展。最近，分子建模的应用已证明能够填补这一空白，为合理研究靶向hAQP4的化合物提供了一个平台。在这篇综述中，我们概述了通过应用分子动力学（MD）和其他互补建模技术在该领域取得的重要进展。本文所呈现的案例研究旨在为对该领域感兴趣并寻求新挑战的计算化学家和生物物理学家提供重要线索。
