DUGi

Càlcul acurat de constants d’acoblament spin-spin i aplicació a la determinació de l’estructura secundària de pèptids

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@10256@@16478

In this work, 12 spin-spin coupling constants (J) obtained experimentally for the Ala3 peptide are used to determine the secondary structure of its central amino acid. For this purpose, a procedure is used that does not assume any main conformation, but considers the entire Ramachandran diagram without limiting it to specific areas. In addition, the algorithm considers the possibility that the value of each observed J is the result of the contribution of different structures/conformations, with the corresponding weights. In order to apply this procedure, it is necessary to know the value of each J for any combination of the dihedral angles ɸ and Ψ of the central amino acid. This is achieved through the Density Functional Theory. Firstly, the 625 structures generated by fixing the dihedral angles ɸ and Ψ are optimized at intervals of 15o at the B3LYP/D95(d,p) level of theory. The values of the 12 J are calculated for each structure with different functionals and basis sets in order to determine their possible effects, and the results are represented as a function of ɸ and Ψ, thus obtaining two-dimensional plots for each J. With these grids it can be observed that one-dimensional Karplus equations are not applicable in general, since with the exception of the constants 3J(C6-H14), 3J(C6-C15) and 3J(C6-C16), the values of J show dependence with the two dihedral angles. The effect of the solvent in the J calculations is also introduced, although it is quickly discarded due to the large deviations obtained with respect to the experimental data. The combination of the functional MPW1WK and the basis set 6-31G-J gives the best results according to the mean deviation (RMSD) with respect to the experimental J values, but the structures that are obtained do not correspond to expected conformations. On the other hand, by calculating the J with the functional MPW1WK and the uncontracted basis set D95 (d,p), the error is slightly higher but the structures obtained fully correspond with alpha helix, beta sheet and polyproline II helix conformations. In this way the functional MPW1WK significantly improves the results obtained with respect to previous reference calculations, where the functional B3LYP with the base D95 (d, p) had been used