Miejsce: aula nr 0142, siedziba przy Banacha 2c
Trying to understand the function of biological macromolecules by analyzing their structural models we easily forget that molecular living systems evolved and function in aqueous environment. It is hard to imagine that the omnipresence of water has not been used by nature as an integral feature of macromolecular machines. In this talk I will give a brief overview of computational studies conducted in my lab that are directed at better understanding of the interplay between biological macromolecules and their environment.
First, I will present the results of our investigation of water structure, kinetics and affinity to buried hydration sites within catalytic subunits of protein kinases. Our simulations indicate that experimentally observed binding cooperativity of the two kinase substrates: ATP and polypeptide chain, is likely to be mediated by an isolated water molecule embedded between the, so called, DFG and YRD kinase motifs. Furthermore, conformational fluctuations of the peptide positioning loop within the kinase catalytic subunit, that are necessary to modulate substrate binding affinity, turn out to be achieved owing to the presence of sequestred, disordered water region.
