Hybrid SCC-DFTB/molecular mechanical studies of H-bonded systems and of N-acetyl-(L-Ala)(n) N '-methylamide helices in water solution

A hybrid quantum mechanical (QM) and molecular mechanical (MM) approach has been developed and used to study the aqueous solvation effect on biologica l systems. The self-consistent charge density functional tight-binding (SCC -DFTB) method is employed to perform the quantum mechanical calculations in the QM part, while the AMBER 4.1 force held is used to perform the molecul ar mechanical calculations in the MM part. The coupling terms between these two parts include electrostatic and van der Waal's interactions. As a test of feasibility, this approach has been first applied to some small systems II-bonded with water molecule(s), and very good agreement with the ab init io results has been achieved. The hybrid potential was then used to investi gate the solvation effect on the capped (L-Ala)(n) helices with n = 4, 5, 8 and 11. (L-Ala)(n) was treated with the SCC-DFTB method and the water mole cules with the TIP3P water model. It has been shown that, in gas phase, the a helices of (L-Ala)(n) are less stable than the corresponding 3(10) helic es. In water solution, however, the alpha helices are stabilized and, compa red with 3(10) helices, the alpha helices have stronger charge-charge inter actions with the surrounding water molecules. This may be explained by the larger dipole moment of alpha helices in aqueous solution, which will influ ence and organize the orientations of the surrounding water molecules. (C) 2000 John Wiley & Sons, Inc.