engleski

Non Covalent Interactions In Protein Complexes

While the electrostatic interactions between the complementary charged proteins increase their interaction, desolvation of the charged and polar amino acid residues destabilizes the protein - protein complex. We studied influence of the electrostatic interactions on formation of the protein complexes between Ras and Rap and their effectors Raf and RalGDS. For this purpose we were solving the Poisson Boltzman equations using the Finite difference method as built in the program UHBD. The electrostatic contribution to desolvation is defined as loss of the electrostatic interaction between protein and solvent upon binding. The calculations revealed negative correlation between binding affinity and desolvation i.e the tightest complexes have the highest desolvation penalty (see the Figure below). However, the correlation between the total electrostatic part of the binding free energy, + +Eeleint, and the measured binding free energy is positive for both RalGDS - Ras, and Raf - Ras complexes. Besides the electrostatic contribution to formation of the protein complexes we also calculated the residue based van der Waals interaction energies and determined the 3D QSAR model for predicting the binding free energy of the new protein mutants. This model enabled us to determine which parts of Ras are responsible for selective binding of its effectors RalGDS and Raf.

proteini; meudjelovanje; modeliranje

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