Computational methods to assist in the discovery of pharmacological chaperones for rare diseases. Issue 5 (21st May 2022)

• Record Type: Journal Article
• Authors: Scafuri, Bernardina; Verdino, Anna; D'Arminio, Nancy; Marabotti, Anna
• Is Part Of: Briefings in bioinformatics. Volume 23:Issue 5(2022)
• Publication Date: 2022-05-21
• Subjects: pharmacological chaperones -- rare diseases -- computational biology -- virtual screening -- molecular dynamics simulations -- stability; Genetics -- Data processing -- Periodicals; Molecular biology -- Data processing -- Periodicals; Genomes -- Data processing -- Periodicals; 572.80285
• DOI: 10.1093/bib/bbac198
• Languages: English
• ISSNs: 1467-5463

Abstract

Abstract: Pharmacological chaperones are chemical compounds able to bind proteins and stabilize them against denaturation and following degradation. Some pharmacological chaperones have been approved, or are under investigation, for the treatment of rare inborn errors of metabolism, caused by genetic mutations that often can destabilize the structure of the wild-type proteins expressed by that gene. Given that, for rare diseases, there is a general lack of pharmacological treatments, many expectations are poured out on this type of compounds. However, their discovery is not straightforward. In this review, we would like to focus on the computational methods that can assist and accelerate the search for these compounds, showing also examples in which these methods were successfully applied for the discovery of promising molecules belonging to this new category of pharmacologically active compounds.