RATIONAL CHOICE OF MOLECULAR-DYNAMICS SIMULATION PARAMETERS THROUGH THE USE OF THE 3-DIMENSIONAL AUTOCORRELATION METHOD - APPLICATION TO CALMODULIN FLEXIBILITY STUDY

We examined the effects of several adjustable parameters for use in mo lecular dynamics simulations of proteins using both standard criteria (radius of gyration, root mean square deviation from starting coordina tes, molecular mechanics energy) and a new description of protein conf ormations by 3-D autocorrelation vectors (3-D ACV). We chose calmoduli n (CaM) as a protein model and analysed 23 simulations using different combinations of the four molecular dynamics parameters studied, such as the dielectric constant (epsilon), the heating phase time (H), the thermal bath coupling time (tau(T)) and the time step size (at). The c orrectness of the various trajectories generated with different parame ter sets was evaluated through geometric analysis and use of a knowled ge-based profile method. It is shown that 3-D ACV combined with multiv ariate statistical analysis provides a convenient way to describe and compare molecular dynamics simulations and constitutes a valuable comp lementary tool to standard methods. Using these methods, comparison of the various simulations performed on CaM indicated that the best in v acuo parameter set was epsilon = 1 x r, H = 15 ps, tau(T) = 0.1 ps and Delta t = 1 fs in fairly good agreement with previous less extensive comparisons of molecular dynamics trajectories.