Ionic Channels as Targets for Drug Design: A Review on Computational Methods

Pharmaceutics

Gregorio Fernández-Ballester¹  Asia Fernández-Carvajal²  José Manuel González-Ros² 

[1] id="af1-pharmaceutics-03-00932">Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Alicante 03202, Spa

关键词: virtual screening;    ion channel;    channelopathies;    quantitative structure;    activity relationships;    homology models;    docking;    pharmacology;    in silico;    in vitro;    drug discovery;    computational approaches;   

DOI  :  10.3390/pharmaceutics3040932

来源: mdpi

【 摘 要 】

Ion channels are involved in a broad range of physiological and pathological processes. The implications of ion channels in a variety of diseases, including diabetes, epilepsy, hypertension, cancer and even chronic pain, have signaled them as pivotal drug targets. Thus far, drugs targeting ion channels were developed without detailed knowledge of the molecular interactions between the lead compounds and the target channels. In recent years, however, the emergence of high-resolution structures for a plethora of ion channels paves the way for computer-assisted drug design. Currently, available functional and structural data provide an attractive platform to generate models that combine substrate-based and protein-based approaches. In silico approaches include homology modeling, quantitative structure-activity relationships, virtual ligand screening, similarity and pharmacophore searching, data mining, and data analysis tools. These strategies have been frequently used in the discovery and optimization of novel molecules with enhanced affinity and specificity for the selected therapeutic targets. In this review we summarize recent applications of in silico methods that are being used for the development of ion channel drugs.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.