DOMAIN MOTIONS IN BACTERIOPHAGE-T4 LYSOZYME - A COMPARISON BETWEEN MOLECULAR-DYNAMICS AND CRYSTALLOGRAPHIC DATA

A comparison of a series of extended molecular dynamics (MD) simulatio ns of bacteriophage T4 lysozyme in solvent with X-ray data is presente d, Essential dynamics analyses were used to derive collective fluctuat ions from both the simulated trajectories and a distribution of crysta llographic conformations, In both cases the main collective fluctuatio ns describe domain motions. The protein consists of an N- and C-termin al domain connected by a long helix, The analysis of the distribution of crystallographic conformations reveals that the N-terminal helix ro tates together with either of these two domains, The main domain fluct uation describes a closure mode of the two domains in which the N-term inal helix rotates concertedly with the C terminal domain, while the d omain fluctuation with second largest amplitude corresponds to a twist ing mode of the two domains, with the N-terminal helix rotating concer tedly with the N-terminal domain, For the closure mode, the difference in hinge-beading angle between the most open and most closed X-ray st ructure along this mode is 49 degrees, In the MD simulation that shows the largest fluctuation along this mode, a rotation of 45 degrees was observed. Although the twisting mode has much less freedom than the c losure mode in the distribution of crystallographic conformations, exp erimental results suggest that it might be functionally important. Int erestingly, the twisting mode is sampled more extensively in all MD si mulations than it is in the distribution of X-ray conformations. (C) 1 998 Wiley-Liss,Inc.