Folding and self-assembly of amyloid beta (AB) peptide are linked to Alzheimer's disease. To understand the initial stage of amyloid-beta peptide aggregation, conformational characteristics of monomers of wildtype (WT) A beta(28-35) and its mutant peptides A30G and A30I were investigated using density functional theory calculations and experimental studies. Monomeric structures and their relative stabilities were obtained on the basis of systematic structural optimization in the gas-phase and in the aqueous medium. Computations were performed by hybrid Hartree-Fock-Density Functional Theory (HF-DFT) at B3LYP/6-31G level. Experimentally, the conformational transitions in the early stages of the octapeptide A)3(2835) and its mutants A30G and A30I in solution were characterized by CD. Thioflavin assay and FRET spectroscopy. Examination of the secondary structures revealed that A beta(28-35) and its mutant monomers exist in random coil conformation in the aqueous medium in agreement with the theoretical predictions, which upon aging is transformed to sheet with different kinetics. This study deals with the structurally important intermediates and it may help to understand the mechanism of amyloid fibril aggregation leading to the onset of Alzheimer's disease. (C) 2010 Elsevier Inc. All rights reserved.