Allosteric Mechanism Of Ca²⁺ Binding Protein

Ca²⁺is the most common second messenger and plays vital physiological roles in variant physiological processes.However,a variety of proteins can not bind Ca²⁺by their own in the physiological processes and cellular responses which regulated by Ca²⁺.Most of them have to interact with the Ca²⁺binding proteins?CaBPs?,and CaBPs which are the signal sensor bind with proteins involved in many signal transduction.So the molecular mechanism of Ca²⁺binding with CaBPs is the inevitable topic of function of the Ca2⁺,also it is the hot issue of many subjects such as biology,chemistry and physics.Calmodulin?CaM?is the representative cellular CaBPs.TMEM16 family is a newly discovered class of calcium activated transmembrane proteins.They have a strong dependence on Ca²⁺and physiological functions.However,the detailed molecular mechanism of the Ca²⁺regulates the state transition of CaBPs is still unclear.Here,we combined Conventional Molecular Dynamics with Targeted Molecular Dynamics.Analyses and compares molecular mechanism of opening Process of CaM.Some valuable results have been obtained.1.The author combined CMD with TMD and it is the creative part of the paper.We achieved the state-transition pathway of CaM which can not be observed by experimental methods.2.Exploreing the concrete mechanism of CaM conformational opening.Ca²⁺play an important part in the conformational change.We analyzed specific changes of hydrogen bond of each area,angle of the two helixes,flexibility and energy in the process,and revealed allosteric process of CaM from these aspects.3.The contribution of two EF-hand to the conformational change of CaM is different.The result was indicative of a sequence of the opening process.And EF-hand 1 undergoes conformational changes prior to EF-hand 2.Ca²⁺induces a conformational change of EF-hand 1,which leads to the allosteric of the EF-hand 2.4.At the same time,the author made elementary research on nhTMEM16 of which is calcium activated transmembrane protein TMEM16 family.The interaction pattern of Ca²⁺binding site amino acid with Ca²⁺was confirmed.And found that the transmembrane protein nhTMEM16 subunit has called on double overall outward expansion trend by principal component analysis.