Lysozyme active-site simulations

In the active-site simulations of lysozyme108 (this chapter, Sect. B.2 above) similar water networks that stabilize charged groups have been observed. To illustrate the dynamics of the formation of such networks, a sequence of stereo plots showing the formation and evolution of a stable pair of positively charged residues is displayed in Fig. 56. The pair consists of (NH2)+ moieties of Arg-61 and Arg-73. The solvated structure evolved from a conformation obtained in a vacuum simulation of lysozyme.108,192 The sequence of plots shows the formation of the water-bridged pair over a time period from t = 0 ps to t 8 ps, which followed dynamical equilibration of the solvent around the fixed vacuum structure of the protein. After 8 ps, the ion-pair structure is stable, but fluctuations in the pattern of hydrogen bonds do occur typical... 

In a molecular dynamics study of native and substrate-bound hen egg-white lysozyme, Post et al. (1986) found the structural features analyzed agreed well with the results of X-ray studies at 0.15-nm (1.5 A) resolution, except for some surface residues. Appreciable differences were found in residue mobilities between the simulations of the native and substrate-bound states in the region of the enzyme that is in direct contact with the substrate and in a region that is distant from the active site cleft. 

The lysozyme molecule was determined to have three antigenic sites with residues coming from widely separated portions of the polypeptide chain the residues proposed as contacting and those synthesized to produce a linear sequence considered as best simulating the active site are seen in Fig. 15. In some instances the peptide synthesized in the reverse direction —for example, using the C-terminal amino acid of the hypothesized determinant as the amino terminus—was used as a control. In some instances, the sequence was considered to have directionality whereas in others it did not. 

To explore these effects more thoroughly, results are presented from stochastic boundary molecular dynamics simulations of the active-site cleft of lysozyme in the presence of aqueous solvent and in vacuum.108 The simulation... 

Figure 43. Solvent effects on local protein motions. The normalized displacement autocorrelation functions are plotted versus time for residues near the active site in lysozyme. Vacuum simulation results are plotted as dashed lines and solvent simulation results are plotted as solid lines for (a) Trp-62 N 1 and (b) Asn-46 Cfl.

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