Research On The Conformation Dynamics Of The Mechanism Of The Mutation Of Neuronal Calcium Sensor Protein Structure In Sports

Exercise can lead to an increase in body temperature,a decrease in pH,and other environmental changes in the body.Some studies have found that the mechanism by which exercise causes the body temperature to rise,which in turn inhibits the body's continued movement,is related to the effect of temperature on the neuronal calcium sensor protein(NCS-1).The effect of exercise-induced changes in body pH on NCS-1may be circumvented.This has become a problem that needs to be solved in the process of comprehensively exploring the effects of exercise on protein structure and function.In recent years,the role of proteins and amino acids in the metabolic mechanism of exercise has received increasing attention from researchers,but it is limited by the time and space and the related costs of research,resulting in difficult to accurately explain the mechanism of action and structural changes associated with exercise-related proteins.And verification,therefore,researchers need to find further breakthroughs in research methods.NCS-1 interacts with different target proteins to achieve a wealth of physiological functions,and changes in the amino acid sequence will play an important role in its function.The amino acid sequence of NCS-1 in humans and other higher animals is compared with this protein in the nematode.The former histidine is substituted for the other amino acids at the 102 and 83 positions of the amino acid sequence,and may therefore reduce the NCS-1 self-sensitivity to pH during synapses.In this study,we investigated the evolution of NCS-1 in different species by using atomic molecular dynamics simulations.We observed that amino acids ARG 102 and Ser 83 were mutated to neutral(R102H and S83H)and acidic(R102H~p and S83H~p)histidines.The impact of the overall protein structure and further exploration of the significance of histidine mutations in NCS-1 resulting from evolution have implications for protein structure and function.In this paper,a total of5?s microsecond molecular dynamics simulation was performed.The main conclusions are as follows:1 The ARG 102 in the amino acid sequence of NCS-1 was mutated to neutral and acidic pH His 102,respectively,and the effects of the two mutations on the structural stability of the protein were found to be different.The R102H mutation at neutral pH did not significantly affect the stability of the protein structure,whereas the acid R102H~p mutation significantly reduced the stability of the NCS-1 structure,indicating that when the acid-base balance of the body is acidic,NCS-1 The stability of the protein structure will be reduced and will therefore affect its function,which in turn inhibits the body's continued movement.2 Neutral R102H and acidic R102H~p mutations also have different effects on the local flexibility of the NCS-1 protein structure.The R102H mutation at neutral pH conditions has less effect on the local flexibility of loop L2,while the R102H~p mutation at acidic pH conditions more significantly reduces the local flexibility of the NCS-1 structure.The greater effect of the acidic pH on its production indicates that when the acid-base balance of the human body is acidic,it may be detrimental to the function of NCS-1.3 Neutral R102H and acidic R102H~p mutations will increase the ductility of loop L3 in NCS-1 to a certain extent,and the more extended loop L3 will lead to the deterioration of NCS-1 function,and thus inhibit the body's continued movement.Therefore,His 102 in other species NCS-1 is mutated to ARG 102 in humans,which objectively achieves circumvention of the mechanism leading to NCS-1 function deterioration.4 Through salt-bridge network analysis and dynamic group network discovery,the neutral R102H mutation and the acid R102H~p mutation have significant effects on the number and probability of salt bridge formation in the salt bridge or between the salt bridges in the segment of the NCS-1 salt bridge network.Both weakened the inter-segmental role of NCS-1 and strengthened the communication within the segment.And when the pH becomes acidic,the link between the N-and C-segments of the protein is further reduced and the interaction is further weakened,and as a result,changes in kinetic characteristics affect the interaction between NCS-1 and the ligand protein.effect.5 The mutation of Ser 83 in the amino acid sequence of NCS-1 to the neutral and acidic pH of His 83,respectively,revealed that both mutations decreased the stability of the protein,indicating that other species of His 83 were mutated to ARG 83 in humans.The NCS-1 function deterioration mechanism was circumvented.Through the study of salt bridge networks of neutral S83H and acidic S83H~p mutants,it was found that when the protein is in an acidic environment,the C-segment intra-domain salt bridge is more strongly destroyed;at the same time,both of the above mutations also affect protein segments.Salt bridges have a destructive effect and will therefore have an adverse effect on the binding of NCS-1 to ligands.6 Mutations alter the similar conformational dynamics of NCS-1 and other NCS family proteins.When the acid-base balance of the human body is acidic,it results in mutant configurational status on the proteins of human NCS-1 and related NCS family proteins.The structural reflection is reduced,and the structural differences between mutants and wild-type NCS-1 may affect the physiological function of the mutant.The mutation of human NCS-1 from His at positions 102 and 83 to ARG and Ser,respectively,compensates for the above-mentioned functional disruption mechanisms,destroying the sensitivity to pH so that the protein can exert normal locomotor inhibition and the temperature rises.Will make NCS-1 inhibit exercise.Therefore,compared with the pH change caused by exercise,the increase in temperature in the internal environment change factor during exercise is a key factor in the NCS-1 function of normal exercise inhibition in the human body.