IFLYSIB   05383
INSTITUTO DE FISICA DE LIQUIDOS Y SISTEMAS BIOLOGICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Conformational changes and diseases. Modeling through molecular dynamics simulations
Autor/es:
S.N. MONACHESI; J.R. GRIGERA; M. C. DONNAMARIA
Lugar:
Santiago del Estero
Reunión:
Congreso; XLIV ReuniĆ³n Anual de la Sociedad Argentina de Biofisica; 2015
Institución organizadora:
Sociedad Argentina de Biofisica
Resumen:
We studied the conformational changes of Glucagon-1(GLP-1) and Exendin-4 (EX4) in aqueous (PH=7) and in physiological solutions (PH=5.3) taken into account the protonation states of the proteins. The interest on these hormones becomes from their glucose-dependent properties related with control of diabetes and obesity. The GLP-1,mammalian protein of 30 aminoacids (AA),has more than 50% of homology with EX4, which is a protein of 39 AA, present at the saliva of Gila Monster. In mammalians the EX4 binds to the same receptor that GLP-1 does, but being more efficient. The protonation states of the proteins are calculated using the ?PROPKA? online program. For modeling the systems we used Molecular Dynamics-MD- which has proved to be a powerful tool to predict properties of molecules. We assumed that the solvent environment ?is? the environment of the protein. The simulations are done in normal conditions of T and P in all solutions. In physiological ones, we used a counterion MD. Through the Root Mean Square Deviation (RMSD) of C the MD convergence and stabilization are verified. It is assumed that in in ?healthy? people, the water MD simulates the proteins, while in diabetics the simulation is made at physiological solution. From the final conformations in water it is seen that in ?healthy? people, the GLP-1 should change the conformations of its terminals. From the results it is seen that in acid media the final conformation of GLP-1 does not allow those changes, but the final conformation of EX4 in acid media does. This may be one reason why EX4 is more efficient in diabetics than the GLP-1 does. MCD and JRG are members of the Research Carriers of CICPBA and of CONICET respectively. JRG is Emeritus Professor at UNLP. SNM is doctoral student of FCE-UNLP. The Authors thank CONICET and UNLP for general support. MCD thanks CICPBA a personnel subsidy of R and D.