MOLECULAR-DYNAMICS SIMULATION OF A 13-MER DUPLEX DNA - A PVUII SUBSTRATE

Parallel version of AMBER 4.I was ported and optimised on the Indian p arallel supercomputer PARAM OpenFrame built around Sun Ultra Spare pro cessors. This version of AMBER program was then used to carry out mole cular dynamics (MD) simulations on 5'-TGACCAGCTGGTC-3', a substrate fo r PVuII enzyme. MD simulations in water are carried out under followin g conditions: (i) unconstrained at 300 K (230 ps); (ii) unconstrained at 283 K (500 ps); (iii) Watson-Crick basepair constrained at 283 K (1 ns); and (iv) Watson-Crick basepair constrained with ions at 283 K (1 .2 ns). In all these simulation studies, the molecule was observed to be bending and maximum distortions in the double helix around was seen around the G7:C7' basepair, which is the phosphodiester bond that is cleaved by PvuII. Analysis of MD simulation with ions carried out for 1.2 ns also pointed out that the conformation of double helix alternat es between a conformation close to B-form and close to A-form. It is a rgued that a bent non-standard conformation is recognised by the PvuII enzyme. The maximum bend occurs at the G7:C7' region, weakening the p hosphodiester bond and allows His48 to get placed in such a fashion to permit the scission through a general base mechanism. The bending and distortion observed is a property of the sequence which acts as a sub strate for PvuII enzyme. This is confirmed by carrying out MD studies on the Dickerson's sequence d(CGCGAATTCGCG)(2) as a reference molecule , which practically does not bend or get deformed.