Investigating the protection effects of pharmaceutical polysaccharides on Interferon beta-۱a against heat stress: A molecular dynamic simulation

Many proteins, including therapeutic proteins, are structurally unstable in the face of multiple stresses, suchas rising temperature. The drug delivery system through polymers increases the therapeutic effect and reducesside effects along with reaching the drug to targeted site at the specified time and the drug is also protected.In this study, the effect of five carbohydrate polymers as alginate, chitosan, heparin, hyaluronic acid andpectin on the stability of interferon beta-۱a protein at ۳۰۰ and ۳۶۳ K was investigated using moleculardynamics simulation methods.The two-dimensional structure of polymers was mapped and optimized with ChemOffice software, thecontents of the resulting PDB file were given to the PRODRG server in order to preparing the topologyparameters of the polymers. The protein coordinate file was also obtained from the Brookhaven ProteinDatabase (http://www.rcsb.org/pdb) in PDB format. The all simulations were performed using Gromacsversion ۵.۱.۱ software and up to ۱۰۰ ns at two temperatures of ۳۰۰ and ۳۶۳ K. Then the results were analyzedusing the different computational tools.Using molecular dynamics simulation, we found that increasing temperature causes protein instability andamong the five polymers investigated, hyaluronic acid and heparin polymers were able to protect the proteinat high temperature.Finally, this study suggests that the preparation of interferon beta-۱a formulations from hyaluronic acid andheparin polymers can be effective in preventing high temperature structure degradation.

Keywords:

molecular dynamics simulation , Gromacs , interferon beta-۱a , polysaccharide polymers , protein-polymer interaction