Domain motions in bacteriophage T4 lysozyme; a comparison between molecular dynamics and crystallographic data

A comparison of a series of extended molecular dynamics (MD) simula- tions of bacteriophage T4 lysozyme in solvent with X-ray data is presented. Essential dynam- ics analyses were used to derive collective fluctuations from both the simulated trajecto- ries and a distribution of crystallographic con- formations. In both cases the main collective fluctuations describe domain motions. The pro- tein consists of an N- and C-terminal domain connected by a long helix. The analysis of the distribution of crystallographic conformations reveals that the N-terminal helix rotates to- gether with either of these two domains. The main domain fluctuation describes a closure mode of the two domains in which the N-termi- nal helix rotates concertedly with the C-termi- nal domain, while the domain fluctuation with second largest amplitude corresponds to a twisting mode of the two domains, with the N-terminal helix rotating concertedly with the N-terminal domain. For the closure mode, the difference in hinge-bending angle between the most open and most closed X-ray structure along this mode is 49 degrees. In the MD simu- lation that shows the largest fluctuation along this mode, a rotation of 45 degrees was ob- served. Although the twisting mode has much less freedom than the closure mode in the distribution of crystallographic conformations, experimental results suggest that it might be functionally important. Interestingly, the twist- ing mode is sampled more extensively in all MD simulations than it is in the distribution of X-ray conformations. Proteins 31:116-127