Applications Of ABEEM??/MM To Study The Structures And Properties Of Urea-water And Urea-dipeptide Systems

Protein denaturation induced by urea is an important phenomenon in biochemistry.Although extensive experimental and theoretical studies on it,there is no consensus about the microscopic mechanism among the scientists.The effect of urea on water structure is also controversial.All-atom molecular dynamics simulation?MD?can obtain microscopic information which is unavailable or difficult to obtain through experiments.At present,MD mainly employs the traditional fixed-charge models and can not reflect the polarization effect.Based on a high-level quantum chemical calculation and the ABEEM??polarization force field model?ABEEM??/MM?,the interactions of urea with water and amino acid dipeptides were studied herein.This thesis mainly includes two parts:???Using QM method and the ABEEM??/MM,the stuctures and properties of[Urea?H₂O?_n]?n=1⁸?and[Urea?AA?₂]?AA=Ala,Val,Gly?systems were studied.???Molecular dynamics simulations on a series of aqueous solution of urea were carried out by using the ABEEM??/MM.???QM method was used to optimize the geometric structures,to caculate the frequency and to obtain stable structures,as well as the binding energies and charge distributions of the stable structures.The results show that there are many types of hydrogen bonds in above systems,among which the types of O_U�H_W-O_W,N_U-H_U...O_A and N_A-H_A...O_U hydrogen bonds are stronger,while the types of O_W...H_U-N_U,C_A-H_A...O_U hydrogen bonds are weaker.The charges of atoms participating in the hydrogen bonds change significantly,and those of the other atoms do not change evidently.Based on the QM results,the potential energy functions of the urea-water/amino acid system were established in the spirit of the ABEEM??fluctuating charge force field model,and the relevant parameters were adjusted and determined.Then the potential energy function were applied to study the structures,hydrogen bonds,and binding energies of the above system.Compared with the QM results,the RMSDs of the ABEEM??/MM results of bond lengths,bond angles and dihedral angles of[Urea?H₂O?_n]are less than 0.026?,3.30�,and 5.00�,respectively;the AADs of hydrogen-bond lengths and hydrogen-bond angles are 0.083?and 2.53�,respectively;the AAD of binding energies is only 1.49 kcal/mol and RRMSD is 5.57%.The RMSDs of the ABEEM??/MM results of bond lengths,bond angles and dihedral angles of[Urea?AA?₂]are less than 0.020?,3.00�,and 15.00�,respectively;the AADs of hydrogen-bond lengths and hydrogen-bond angles are 0.151?and 5.20�;the AAD of binding energies is 0.86 kcal/mol and RRMSD is 12.80%.The linear correlation coefficients of charge distributions between ABEEM??/MM and HF/STO-3G results are between 0.94 and 1.00.All of the above results are better than those of the OPLS/AA force field.???Under NVT ensemble,ABEEM??/MM/MD was performed to study the aqueous urea system of 0.55M,0.99M,1.99M,2.99M,and 3.54M.The preliminary results show that after 120 ps,all the different systems reach the stable state.The concentration of urea has little effect on the structure of aqueous solution.The first peak of the RDF between O_W?oxygen of water?and H_W?hydrogen of water?and between O_W and O_W is about 2.0?and 3.0?respectively,and it between O_U?oxygen of urea?and H_W is about 2.2?,whch is the same as first peak of the RDF between H_U?hydrogen of urea?and O_W.The first peak of the RDF between O_U and O_W appears around 3.1?.The hydration numbers of urea in the first hydration shell are 5.9,7.0,6.8,6.4 and 6.9,respectively.