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http://dx.doi.org/10.1021/bi00109a009

has been cited by the following article:

• TITLE: Conformational flexibility of the pharmacologically important insulin analogues

  AUTHORS: Olga Ksenofontova, Vasily Stefanov

  KEYWORDS: Insulin Analogues; Conformational Flexibility; Molecular Dynamics Simulation Study

  JOURNAL NAME: Advances in Biological Chemistry, Vol.3 No.5, October 30, 2013

  ABSTRACT: Understanding the conformational flexibility of the insulin drugs is of great importance for the treatment of diabetes mellitus. Once in the body, the drug must have a certain degree of mobility within a specified period of time for the manifestation of its pharmacological properties. This mobility ensures conformational states necessary for binding with the insulin receptor and activating specific biological processes. In this work we investigated conformational flexibility of the pharmacologically important insulin analogues—insulin lispro, insulin aspart, insulin glulisine, and insulin glargine, using the molecular dynamics simulation method. This study provides new insight into the nature of behaviour of A-and B-chains. It has been found out that B-chain substitutions result in rapid acting, while long-lasting action can be achieved by substitutions in both chains. The results of this study can be used for development of new insulin-based antidiabetic drugs.