Molecular dynamics simulations of the isolated domain 1 of annexin I

Annexin molecules consist of a symmetrical arrangement of four domains of i dentical folds but ver, different sequences. Nuclear magnetic resonance (NM R) experiments on the isolated domains of annexin I in aqueous solution hav e indicated that domain 1 retains its native structure whereas domain 2 unf olds. Therefore these two domains constitute interesting models for compara tive simulations of structural stability using molecular dynamics. Here we present the preliminary results of molecular dynamics simulations of the is olated domain 1 in explicit water at 300 KI using two different simulation protocols. For the first, domain 1 was embedded in a 46 Angstrom cubic box of water. A group-based non-bonded cut-off of 9 Angstrom with a 5-9 Angstro m non-bonded switching function was used and a 2 fs integration stop. Bonds containing hydrogens were constrained with the SHAKE algorithm. These cond itions led to unfolding of the domain within 400 ps at 300 K. In the second protocol, the domain was embedded in a 63 Angstrom cubic box of water. An atom-based non-bonded cut-off of 5-12 Angstrom using a force switching func tion for electrostatics and a shifting function for van der Waals interacti ons were used with a 1 fs integration step. This second protocol led to a n ative-like conformation of the domain in accord with the NMR data which was stable over the whole trajectory (similar to 2 ns). A small, bur well-defi ned relaxation of the structure, from that observed for the same domain in the entire protein, was observed. This structural relaxation is described a nd methodological aspects are discussed.