1 Max-Planck-Institute of Molecular Physiology, Department Structural Biology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
The Rho GTPases constitute a large family of small GTP binding proteins that control diverse cellular functions like the actin cytoskeleton, cell polarity, gene expression, microtubule dynamics and vesicular trafficking . The understanding of their function at molecular level belongs therefore to the important tasks of molecular biology. Second reason why Rho GTPases attract the attention of scientists is that their abnormal activation plays a role in tumour invasion and metastasis  and in a diseases like the hypertension or bronchial asthma .
We will present the results of molecular modelling methods applied to some particular problems concerning Rho GTPases. First we will discuss the model of RhoA cycle at atomic level constructed on the base of known crystal structures of corresponding sub-states of the cycle. Then we will demonstrate the importance of global dynamics of proteins in their function that emerged from the functional analysis of different Rac1 isoforms . Finally we will report the outcomes from the in-silico virtual screening focused in this case on the modifications of nucleotides that would increase their affinities towards the Cdc42 and the compounds capable to abolish the interaction of RhoA with its effector protein ROCKI and the interaction of Rac1 with its guanine nucleotide exchange factor Tiam1.
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