Molecular Dynamics Simulations Study The Structural And Dynamic Characteristics Of Hydrated Proteins

Staphylococcal nucleases(SNase)have a strong ability to disrupt DNA structure and may resolve some of the problems caused by autoimmune diseases that block the clearance of NETs(Neutrophil Extracellular Traps).The W140-centered mediated formation of the carbon terminal cluster plays an important role in the folding properties,stability and activity of the SNase conformation,while mutations in the surrounding K110 or E129 or K133 may lead to structural instability,causing changes in hydration dynamics and function.Hydration dynamics is critical to protein structural stability and biological function,but the way in which the two interact is far from being clearly revealed.In order to explore these issues,we took SNase(SN0)as the model,based on the theory of molecular dynamics,and used GROMACS software to simulate hydrated SNase protein under the framework of protein dynamics transition(PDT)(150K-300K)and different mutation systems SN1(K110A,single mutation),SN2(K110A&E129A,double mutation)and SN3(K110A&E129A&K133A,triple mutation),analyzed protein structure fluctuations,protein-water surface structure and hydrogen bond dynamics characteristics.It is of great significance for revealing the hydration layer dynamics how to influence protein dynamics from the molecular level,and provides structural data for explaining the relationship between structure and functional activity,laying the foundation for future drug development for autoimmune diseases.The main conclusions are as follows:Using molecular dynamics methods to explore the influence of temperature on the structure and dynamics of SNase protein,we found that the protein maintained a more conservative conformation at low temperatures,the movement of protein atoms was small,and the arrangement of water molecules at low temperatures was orderly,there were more hydrogen bonds formed between water and protein.The protein structure fluctuation began to increase at 210K,and the hydration characteristics also changed at210K.When the temperature increased,the hydrogen bond was lost about 40%.The thermal motion of water molecules on the picosecond time scale began to dominate,and the average energy barrier gradually fell within the thermal fluctuation range,and the previously established hydrogen bond between protein and water became unstable.When it was higher than 210K,hydrated water molecules had the same ability and opportunity to made hydrogen bonds with protein and other water molecules,which may eventually activate proteins under the influence of the dynamics of large-scale hydrogen bond networks.The strong coupling between protein and water was confirmed,hydrogen bonding acted an important role in activating protein activity.Using molecular dynamics methods to explore the effects of mutations on the structure and dynamics of SNase protein,we found that as the number of alanine mutations increased from SN0 to SN3,random coils had increased,which made the flexibility greatly changed when K133 was mutated to alanine.Mutation-induced changes in the charge environment had a strong influence on hydration dynamics,with a biphasic distribution of relaxation times.Mutations from SN1 to SN3 gradually replaced residues containing larger side chains with alanine with only CH₃groups.Smaller side chains mean that water molecules had more free and movable space.Water molecules near the protein surface constantly adjusted their positions and directions to adapted to the dynamic reconstruction of the hydrogen bond network they participated in.In an environment where the residues were more charged,water was more restricted.However,when it was mutated to a hydrophobic environment,there were faster hydrodynamics due to the enhanced water-water interaction.The enhancement of active site hydration dynamics may facilitate the enhancement of protein activity and lay the foundation for studying the role of hydration dynamics in achieving protein function.