A theoretical study of biologically important molecules

Abstract

Interesting aspects of a few biologically important molecules such as penicillin G, acetylcholine (ACh), acetylcholinesterase (AChE), vitamin B6 and nucleotidea?|metal complexes have been studied by means of quantum mechanical techniques. Alkaline hydrolysis of Penicillin G shows that incorporation of the amide side chain and acid group increases the reaction barrier, whereas, the thiazolidine ring lowers the barrier. AChE-catalyzed hydrolysis of the neurotransmitter ACh shows that the stepwise mechanism is kinetically more favourable than the cooperative mechanism. Cation-I? interaction between the positively charged ammonium head of ACh and the aromatic amino acid residues of AChE are believed to assist the former in reaching the deep seated active site of the enzyme. Our study shows that the optimum distance of cation-I? interaction range from 4.59 ?? to 4.87 ?? and charge transfer seems to play a vital role in stabilizing complexes with cation-I? interactions. Complexes with greater charge transfer were found to have larger binding energies. Study of tautomeric equilibria of a variety of 3-hydroxypyridine derivatives including pyridoxal-5A'-phosphate, the active form of vitamin B6, shows that the neutral (hydroxy) form is more stable than the zwitterionic (oxo) form in the gas phase, nonpolar and aprotic polar media while a reversal of tautomeric equilibrium is predicted in an aqueous medium. A combination of both explicit and implicit solvation models seems to be necessary to fully account for the effects of aqueous solvation.