Effect of piratoxin II and acutohaemolysin phospholipase (PLA2) proteins on myristic fatty acid--an ONIOM and DFT study.

A theoretical investigation on the interaction of myristic fatty acid (M) with Acutohaemolysin and Piratoxin-II of PLA2 family is performed using two layered ONIOM (B3LYP/6-31G*: UFF) method. The results predict that though proteins show revulsion to incoming fatty acid, the interaction of the phenyl ring of Phenylalanine restricts the passage of M through the channel. To unveil the nature of interaction of M, quantum chemical studies are carried out on the palindromic tripeptides Alanine-Phenylalanine-Alanine (AFA) and Alanine-Valine-Alanine (AVA) present in Acutohaemolysin and Piratoxin-II at B3LYP/6-311G** level of theory. The mode of interaction of the fatty acid with protein is electrostatic, confirmed further through molecular electrostatic potential (MEP) maps. The AFA shows stronger interaction than AVA, validating the impact of mutation on catalytic activity. Further such strong interaction and hence the higher probability of prohibition for catalytic activity exists only when the fatty acid interacts at the center of phenyl ring than at its edges. The preferred secondary structural configuration and conformational properties of AVA and AFA also validate the strong interaction of fatty acid with Phenylalanine. In general, this theoretical investigation shows that the loss of catalytic activity would take place only when fatty acid interacts at the center of phenyl ring.