Design and molecular dynamic simulation of a new double-epitope tolerogenic protein as a potential vaccine for multiple sclerosis disease

Abstract

One of the debilitating diseases affecting the central nervous system is multiple sclerosis (MS). As there is no definitive treatment for MS, researchers have mainly consented with optimization of strategies which slows down the progression of the disease such as specific auto-antigens tolerance induction. In this regard, the aim of this study was design of a new double-epitope protective vaccine based on interleukin (IL)-16-neuroantigens fusion proteins. First, we selected highly antigenic epitopes of myelin basic protein (MBP) (aa 84-104) and myelin oligodendrocyte glycoprotein (MOG) (aa 99-107) from available literature and our bioinformatics analysis. The correct cleavage of our constructs and major histocompatibility complex class II binding affinities of cleaved epitopes were checked and evaluated using Pepcleave and IEDB servers, respectively. Then, different combination of MOG and MBP epitopes with or without fusion to C-terminal active part of IL-16 were designed as constructs. Afterward, Modeller and Gromacs softwares used for the investigation of the MBP, and MOG epitopes antigenicity in these constructs. The results of molecular dynamics simulations showed that IL-16 in MOG + linker + MBP + IL-16 construct does not interfere with final epitopes antigenicity of MOG + linker + MBP construct. To sum up, the construct with IL-16 is suggested as a new double-epitope tolerogenic vaccine for prevention and amelioration of MS in human.

Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus

“…The RMSF profile showed the presence of a highly fluctuating N-terminal region at the beginning of the simulation. This result was consistent with previous studies where immunoinformatics of vaccine–receptor complex stabilization was achieved within a similar time-scale using MDs 59 , 73 , 90 , 91 . The rGyr measures the 'extendedness' of a ligand, and is equivalent to its principal moment of inertia.…”

The effect of mutation on neurotoxicity reduction of new chimeric reteplase, a computational study

“…To analyze docking complexes, the interaction between ATD and each reteplase was analyzed after simulation. These analyses are including root mean squared fluctuation (RMSF), root means squared deviation (RMSD), average solvent accessible surface area (SASA), the radius of gyration (Rg), the minimal distance between two proteins in each docking complex, number of contacts between residues of two proteins in each docking complex, the total number of intermolecular hydrogen bonds formed between two proteins ( 23 24 25 ). Also, The molecular mechanics Poisson-Boltzmann surface area (MMPBSA) method was used which has been broadly applied as an effective and trustworthy free energy simulation method for the assessment of molecular interactions like protein-ligand binding or protein-protein interactions ( 26 ).…”

Interactions and effects of food additive dye Allura red on pepsin structure and protease activity; experimental and computational supports

“…To this end, the topological information of the ligand was obtained using the ATB server ( 22 )and the simulations were done using Gromacs 5.1 package in the Gromos53a6 force field ( 22 23 ). The box was then solvated by SPC/E water molecules and in order to completely neutralize the system, enough counter ions were added ( 24 ). The system energy was minimized using the steepest descent algorithm ( 25 ).…”