title: Human Aquaporin-4 and Molecular Modeling: Historical Perspective and View to the Future.
abstract: 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.
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Via Orabona, 4, University of Bari "Aldo Moro", 70126 Bari, Italy. giuseppe.mangiatordi@uniba.it.
authors.forename: Giuseppe Felice
authors.initials: GF
authors.lastname: Mangiatordi
authors.affiliation: Institut de Recherche de Chimie Paris CNRS Chimie ParisTech, PSL Research University, 11 rue P. et M. Curie, F-75005 Paris, France. domenico.alberga@chimie-paristech.fr.
authors.forename: Domenico
authors.initials: D
authors.lastname: Alberga
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Via Orabona, 4, University of Bari "Aldo Moro", 70126 Bari, Italy. daniela.trisciuzzi@uniba.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Trisciuzzi
authors.affiliation: INFN-Sez. di Bari and Dipartimento di Medicina Clinica e Sperimentale, University of Foggia, Viale Pinto, 71122 Foggia, Italy. gianluca.lattanzi@unifg.it.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Lattanzi
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Via Orabona, 4, University of Bari "Aldo Moro", 70126 Bari, Italy. orazio.nicolotti@uniba.it.
authors.forename: Orazio
authors.initials: O
authors.lastname: Nicolotti
mesh_terms: D051401:Aquaporin 4 / Q000737:chemistry* / Q000266:history* / Q000378:metabolism; D049674:History, 21st Century; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009471:Neuromyelitis Optica / Q000378:metabolism / Q000473:pathology; D011487:Protein Conformation
chemical_list: D051401:Aquaporin 4; D007074:Immunoglobulin G
keywords: druggability; epitope; gating mechanisms; human aquaporin-4 (hAQP4); molecular dynamic (MD) simulations; neuromyelitis optica (NMO)-IgG binding