Hybrid SCC-DFTB/molecular mechanical studies of H-bonded systems and ofN-acetyl-(L-Ala)nN?-methylamide helices in water solution

Abstract

A hybrid quantum mechanical (QM) and molecular mechanical (MM) approach has been developed and used to study the aqueous solvation effect on biological 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 field is used to perform the molecular 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 H-bonded with water molecule(s), and very good agreement with the ab initio results has been achieved. The hybrid potential was then used to investigate 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 molecules with the TIP3P water model. It has been shown that, in gas phase, the α helices of (L-Ala)n are less stable than the corresponding 310 helices. In water solution, however, the α helices are stabilized and, compared with 310 helices, the α helices have stronger charge–charge interactions with the surrounding water molecules. This may be explained by the larger dipole moment of α helices in aqueous solution, which will influence and organize the orientations of the surrounding water molecules. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 78: 459–479, 2000