| Summary: | 碩士 === 國立清華大學 === 生命科學系 === 90 === Snake venoms make people die often and snakes only live by them. They consist of cardiotoxin (CTX), neurotoxin, and phospholipase A2 (PLA2). From the published reports, there are five kinds of venom proteins in the CTX molecules found in Taiwan cobra (Naja naja atra) venom, and they were named CTX A1~A5. Next, CTX proteins have been classified into two types, P-type and S-type, which are distinguished by the presence of Pro30 and Ser28, respectively, near the tip of loop II.
An interesting phenomenon called "bound water" was found in recent reports. By the NMR experiments, this water molecule exists in loop II of CTX A3 protein, which is a P-type protein. It is possible for its function to form a hydrogen-binding network in loop II, and this network may keep the above β-sheet structures stable.
In this thesis, we study this phenomenon by molecular dynamics simulations. We first mutate Pro30 to Gly by using the empirical valence bond model. And then by using the free energy perturbation method, we calculate the free energy differences. From the point of view of the thermodynamic cycle, we can get the values of ΔΔG, the changes of the Gibbs free energy differences. The meaning of ΔΔG is to discuss the effects of mutation of side chains with bound water on protein. Finally, after comparing the results of P-type proteins with S-type ones, we suggest that the amino acid, Pro30, may be a "key" for the bound water. Namely, although Pro30 is not directly bound with the bound water by hydrogen bonds, this residue still affects this bound water molecule.
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