作者
Wei-Tse Hsu, Dominique A Ramirez, Tarek Sammakia, Zhongping Tan, Michael R Shirts
发表日期
2022/4
期刊
Journal of computer-aided molecular design
卷号
36
期号
4
页码范围
313-328
出版商
Springer International Publishing
简介
Insulin has been commonly adopted as a peptide drug to treat diabetes as it facilitates the uptake of glucose from the blood. The development of oral insulin remains elusive over decades owing to its susceptibility to the enzymes in the gastrointestinal tract and poor permeability through the intestinal epithelium upon dimerization. Recent experimental studies have revealed that certain O-linked glycosylation patterns could enhance insulin’s proteolytic stability and reduce its dimerization propensity, but understanding such phenomena at the molecular level is still difficult. To address this challenge, we proposed and tested several structural determinants that could potentially influence insulin’s proteolytic stability and dimerization propensity. We used these metrics to assess the properties of interest from aggregate molecular dynamics of each of 12 targeted insulin glyco-variants from multiple wild-type crystal …
学术搜索中的文章
WT Hsu, DA Ramirez, T Sammakia, Z Tan, MR Shirts - Journal of computer-aided molecular design, 2022