Mathematical modelling of electrostatic fluctuations in subtilisin active site.

The intensities of electrostatic fluctuations in subtilisin active site generated by conformational motion of charged side chains, polar side chains and peptide bonds of the main chain are calculated. The comparative analysis of all these fragments reveals that there are few of them which make the main contribution to the total value of the intensity, which has been found to be approximately 10(7) g.cm-1.s-2. These are Ser 125, Thr 220 and peptide bonds of aminoacids 125-126, 218-219. Our present analysis enables us to compare the relative contribution of different fragments but we do not pretend to obtain precise absolute values. The reason for this is the lack of the detailed selective information on the mean-square amplitudes and correlation times of conformational motion of the fragments and on the values of local dielectric constants in the interior of subtilisin. The possibility for electrostatic fluctuations in enzyme active site to be an efficient nonspecific source of substrate activation is discussed.