The guanine nucleotide-binding proteins are responsible for various cellular processes in eukaryotic cells,including heterotrimeric G-proteins and members of Ras-related superfamily.The Ras protein has the catalytic activity of hydrolyzing the guanosine triphosphate(GTP)to guanosine diphosphate(GDP),which is called the GTPase.The cycling of hydrolysis of GTP and GDP in Ras plays an important role in the signal processes involved in cell.A malfunction of Ras protein can lead to uncontrolled cell proliferation,which eventually causes tumors.To take insight in the function of Ras family in controlling signal processes,an elaborate investigation of the hydrolysis mechanism of GTP in Ras protein needs to be performed at the atomic level with a combination of experimental and theoretical methods.Currently,a big amount of experimental data associated with the specific vibrations of P-O bonds in GTP measured from Fourier-transformed infrared spectroscopy(FTIR)is available,which provide the experimental implications of hydrolysis mechanism of GTP.We therefore used QM/MM simulations to calculate the spectra and the normal vibrational modes GTP in various environments such as the aqueous solution,Ras and RasGAP complex.The simulation results show the GTPs adopt distinctive structural conformations and coordination patterns with Mg2+ cations in different environments.The calculated specific vibrational frequencies of bonds in GTP are in good agreement with the experimentally measured difference spectra,providing a very good validation of conformations obtained by the simulations.For the first time,we suggest band assignments of the vibrational modes of GTP in Ras below 800cm-1 by comparison of calculated and experimental spectra.