Molecular dynamics simulation lysozyme

Hayward, S., Kitao, A., Berendsen, H.J.C. Model-free methods to analyze domain motions in proteins from simulation A comparison of normal mode analysis and molecular dynamics simulation of lysozyme. Proteins 27 (1997) 425-437. 

The first reported molecular dynamics simulations of carbohydrates began to appear in 1986, with the publication of studies of the vacutim motions of a-D-glucopyranose (9), discussed below, and the dynamics of a hexa-NAG substrate bound to lysozyme (IQ), which are described in greater detail in the chapter by Post, et al. in this voltime. Since that time, simulations of the dynamics of many more carbohydrate molecules have been undertaken. A number of these studies are described in subsequent chapters of this voltime. The introduction of this well developed technique to problems of carbohydrate structure and function could contribute substantially to the understanding of this class of molecules, as has been the case for proteins and related biopolymers. 

Stocker U, van Gunsteren WL (2000) Molecular dynamics simulation of hen egg white lysozyme a test of the GROMOS96 force field against nuclear magnetic resonance data, Proteins Struct Fund Genet, 40 145-531... 

Smith, L.J., Mark, A. E., Dobson, C.M. and Gursten, W. F. (1998) Molecular dynamic simulation of peptide fragments from hen lysozyme insight into non-native protein conformation./. Mol. Biol. 280, 703-719. 

These CMD results are still qualitative and somewhat conflicting with the available experimental data [55], largely because of the simplified models used for the surfaces and more certainly due to difficulties in choosing suitable potential functions for the simulations. However, recently, molecular dynamic simulations of the hen egg-white lysozyme-Fab D1.3 complex have been reported both the crystal state and the complex in solution were studied [35]. The findings are consistent with the observation by various experimentalists of a reduced water mobility in a region extending several angstroms beyond the first hydration layer [54-57], as reported also from CMD simulations [60]. 

Lysozyme is a key system in the development of our understanding of the structure and function of proteins. It was the first enzyme whose x-ray structure was determined at high resolution (Blake et al. 1965), one of the earliest enzymes for which a detailed reaction mechanism was proposed and one of the test systems for molecular dynamics simulations. In this section, we review some of the simulation studies of lysozyme with emphasis on the reaction mechanism and on the large scale domain motion involved in the mechanism. 

Smith, P., R. Brunne, A. Mark and W. vanGunsteren. (1993). Dielectric properties of trypsin inhibitor and lysozyme calculated from molecular dynamics simulations. Journal of Physical Chemistry. 97 2009-2014. 

Figure 13. Calculated and experimental rms fluctuations of lysozyme. Backbone averages are shown as a function of residue number, and were obtained (a) from a molecular dynamics simulation and (b) from X-ray temperature factors without correcting for disorder contributions. (From Ref. 192.)...

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... 

The correlation function, <-P2[am(0) ( )]>. provides a measure of the internal motions of particular residues in the protein.324 333 Figure 46 shows the results obtained for Trp-62 and Trp-63 from the stochastic boundary molecular dynamics simulations of lysozyme used to analyze the displacement and velocity autocorrelation functions. The net influence of the solvent for both Trp-62 and Trp-63 is to cause a slower decay in the anisotropy than occurs in vacuum. In vacuum, the anisotropy decays to a plateau value of 0.36 to 0.37 (relative to the initial value of 0.4) for both residues within a picosecond. In solution there is an initial rapid decay, corresponding to that found in vacuum, followed by a slower decay (without reaching a plateau value) that continues beyond the period (10 ps) over which the correlation function is ex-... 

An important question regarding peptides and proteins is concerned with the equilibria among several conformational states. It has been suggested that enzyme function may be linked to the occurrence of particular conformations in solution.24 377 A mechanism recently proposed for the hydrolysis of oligosa-charides by the enzyme lysozyme, for example, is based on the observation of specific substrate and enzyme sidechain conformations in a molecular dynamics simulation of a lysozyme-substrate complex.378 Also, local conformational equilibria and the barriers between conformations are important in determining the rates and mechanisms of folding and rebinding processes. 

An additional factor to consider is the magnitude of the anharmonic contribution to the entropy of proteins. Analyses of molecular dynamics simulations have demonstrated that the major anharmonic contributions can be ascribed to multiple conformations for individual atoms.195 In BPTI and lysozyme, an estimate of the change in entropy due to these effects (e.g., 89 atoms in lysozyme have multiple wells) yields a correction of less than 2% for the classical entropy. Thus multiple conformations appear not to be important for the residual entropy at ordinary temperatures.389 However, near absolute zero (1 to 2 K) there are data that suggest that several minima ( tunneling states ) contributes significantly to the entropy.390... 

C. B. Post, B. R. Brooks, M. Karplus, C. M. Dobson, P. j. Artymiuk, J. C. Cheetham, and D. C. Phillips,. Mol. Biol., 190, 455 (1986). Molecular Dynamics Simulations of Native and Substrate-Bound Lysozyme. A Study of the Average Structures and Atomic Fluctuations. 

Buck, M., Karplus, M. Internal and overall peptide group motion in proteins Molecular dynamics simulations for lysozyme compared with results from X-ray and NMR spectroscopy. J. Am. Chem. Soc. 1999, 121, 9645-58. 

Lerbret A, Affouard Fdr, Hedoux A, Krenzhn S, Siepmann Jr, BeUissent-Funel M-C, Descamps M (2012) How strongly does trehalose interact with lysozyme in the solid state Insights from molecular dynamics simulation and inelastic neutron scattering. J Phys Chem B 116 11103— 11116... 

E. T. Olejniczak, C. M. Dobson, M. Karplus, and R. M. Levy, /. Am. Chem. Soc., 106, 1923 (1984). Motional Averaging of Proton Nuclear Overhauser Effects in Proteins. Predictions from a Molecular Dynamics Simulation of Lysozyme. 

Higher Oligosacdiarides and C-Glyco es. - Following the previous section, not only di-, but tri- and tetrasaccharide complexes of rainbow trout lysozyme have been characterized by X-ray analysis. The orientation of the (a 1- 6) mannosyl arm of a heptasaccharide and hexasacchatide (and disaccharide fragments) has been studied by molecular dynamics simulations and compared with protein-carbohydrate complex crystal structures. ... 

One of the main attractions of normal mode analysis is that the results are easily visualized. One can sort the modes in tenns of their contributions to the total MSF and concentrate on only those with the largest contributions. Each individual mode can be visualized as a collective motion that is certainly easier to interpret than the welter of information generated by a molecular dynamics trajectory. Figure 4 shows the first two normal modes of human lysozyme analyzed for their dynamic domains and hinge axes, showing how clean the results can sometimes be. However, recent analytical tools for molecular dynamics trajectories, such as the principal component analysis or essential dynamics method [25,62-64], promise also to provide equally clean, and perhaps more realistic, visualizations. That said, molecular dynamics is also limited in that many of the functional motions in biological molecules occur in time scales well beyond what is currently possible to simulate. 

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