A MOLECULAR SWITCH FOR BIOCHEMICAL LOGIC GATES - CONFORMATIONAL STUDIES

This report presents the computer-assisted design of a molecular switc hing element, in which a molecular switch regulates the enzymatic acti vity of Ribonuclease A (RNase A). The molecular switch, an appropriate ly modified amino acid residue, is constructed with an electron donor group and an electron acceptor group, connected to one another with a conjugated double bond bridge. The switching mechanism is based on the azonium-hydrazo tautomerization, by which a charge separation induced in the excited state causes a rearrangement of the molecular electron ic structure, resulting in the exchange of locations of single and dou ble bonds. This rearrangement of bonds leads to different three dimens ional conformations of the switch. Using the electrostatically driven Monte Carlo (EDMC) method and the empirical conformational energy prog ram for peptides (ECEPP/3) potential energy function, we carried out a n exhaustive search of the conformational space of the switching eleme nt. The results of these calculations reveal two sets Of conformations : in one set the access to the active site of the enzyme is preferenti ally blocked, while in the other set the active site is preferentially accessible. Integration of the designed element into biochemical logi c gates operating under the rules of threshold value, and experimental implementation of this system, are considered. (C) 1996 Elsevier Scie nce Limited