title: A molecular simulation study of the protection of insulin bioactive structure by trehalose.
abstract: Biopharmaceuticals are proteins with a crucial role in the treatment of many diseases. However, these protein medicines are often thermally labile and therefore unsuitable for long-term application and storage, as they tend to lose their activity under ambient conditions. Desiccation is one approach to improving protein stability, but the drying process itself can cause irreversible damage. In the current study, insulin was chosen as an example of a thermally sensitive biopharmaceutical to investigate whether the disaccharide, trehalose, can prevent loss of structural integrity due to drying. The experiment was performed using replica exchange molecular simulation and Gromacs software with a Gromos96 (53a6) force field. The results indicate that trehalose preserves the bioactive structure of insulin during drying, consistent with the use of trehalose as a protectant for thermally sensitive biopharmaceuticals. For instance, at the water content of 1.77%, insulin without any protectants yields the highest RMSD value as 0.451 nm, then the RMSD of insulin in presence of trehalose only ca. 0.100 nm.
authors.affiliation: Institute of Biothermal Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China, dxli75@126.com.
authors.forename: Daixi
authors.initials: D
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Huaxing
authors.initials: H
authors.lastname: Yu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhai
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Baisong
authors.initials: B
authors.lastname: Guo
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Yang
authors.forename: Baolin
authors.initials: B
authors.lastname: Liu
mesh_terms: D000465:Algorithms; D002626:Chemistry, Pharmaceutical; D003890:Desiccation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology; D007328:Insulin / Q000737:chemistry* / Q000494:pharmacology; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012984:Software; D013329:Structure-Activity Relationship; D013696:Temperature; D014199:Trehalose / Q000737:chemistry*
chemical_list: D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D014199:Trehalose