ABSTRACT
The growth of cells is controlled by stimulatory or inhibitory factors. More than twenty different families of polypeptide growth factors have been structurally and functionally characterized. Basic fibroblast growth factor (bFGF) of the fibroblast growth factor family was characterized in 1974 as having proliferative activity for fibroblastic cells. The inhibitory effects of ethanol on cell proliferation result from interference with mitogenic growth factors (e.g., bFGF, EGF and PDGF). In order to better understand the mode of action of bFGF, particularly regarding the influence of ethanol on the biological activity of bFGF, three recombinant bFGF mutants were produced (M6B-bFGF, M1-bFGF and M1Q-bFGF). In the present study, wild bFGF and these mutants were examined by molecular dynamics simulations in systems consisting of a solute molecule in ethanol solution at 298 K and physiological pH over 4.0 ns. The hydrogen bonds, the root mean square deviations and specific radial distribution functions were employed to identify changes in the hydrogen bond structures, in the stability and in the approximation of groups in the different peptides to get some insight into the biological role of specific bFGF regions. The detailed description of the intramolecular hydrogen bonds, hydration, and intermolecular hydrogen bonds taking place in bFGF and its mutants in the presence of ethanol established that the residues belonging to the beta5 and beta9 strands, especially SER-73(beta5), TYR-112(beta9), THR-114(beta9), TYR-115(beta9), and SER-117(beta9), are the regions most affected by the presence of ethanol molecules in solution.