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.  [c.35]

Hayward, S., Berendsen, H.J.C. Systematic analysis of domain motions in proteins from conformational change New results on citrate synthase and T4 lysozyme. Proteins 30 (1998) 144-154.  [c.36]

In an early study of lysozyme ([McCammon et al. 1976]), the two domains of this protein were assumed to be rigid, and the hinge-bending motion in the presence of solvent was described by the Langevin equation for a damped harmonic oscillator. The angular displacement 0 from the equilibrium position is thus governed by  [c.72]

McCammon et al. 1976] McCammon, J.A., Gelin, B.R., Karplus, M., Wolynes, P.G. The hinge-bending mode in lysozyme. Nature 262 (1976) 325-326  [c.77]

Extraction of Bound Xenon from Mutant T4-Lysozyme  [c.141]

We have chosen to study the extraction of the xenon atom from its binding site inside the hydrophobic cavity in mutant T4 lysozyme as a simple system in which to model the ligand extraction process. The internal binding site in this mutant is hydrophobic and excludes water as a result, an important source of friction in the extraction of a ligand (the simultaneous entry of water molecules) is absent. On the other hand, this system shares with the avidin-biotin system the requirement for a distortion of the geometry at the exit point in order to permit the ligand to escape. With long, but feasible, simulations it may therefore be possible to approach conditions of very slow extraction and hence small friction, in which the extraction force is dominated by the change in free energy (Cf. eq. 4). We describe first the interactive simulations in which we located an exit path for the xenon atom, and then the results of a scries of extractions performed at different rates.  [c.141]

Eriksson, A. E., Baase, W. A., Wozniak, J. A., Matthews, B. W. A cavity-containing mutant of T4 lysozyme is stabilized by buried benzene. Nature 355 (1992) 371-373  [c.146]

Hermans, J., Wang, L. Inclusion of loss of translational and rotational freedom in theoretical estimates of free energies of binding. Application to a complex of benzene and mutant T4-lysozyme. J. Am. Chem. Soc. 119 (1997) 2707-2714  [c.146]

Morton, A., Baase, W. A., Matthews, B. W. Energetic origins of specificity of ligand binding in an interior nonpolar cavity of T4 lysozyme. Biochemistry 34 (1995) 8564-8575.  [c.147]

The critical factor for any method involving an approximation or an extrapolation is its range of application. Liu et al. [15] demonstrated that the approach performed well for mutations involving the creation or deletion of single atoms. The method has also been successfully applied to the prediction of the relative binding affinities of benzene, toluene and o-, p-, and m-xylene to a mutant of T4-lysozyme [16]. In both cases, however, the perturbation to the system was small. To investigate range over which the extrapolation may  [c.159]

Tanford, C., Roxby, R. Interpretation of protein titration curves Application to lysozyme. Biochem. 11 (1972) 2192-2198.  [c.195]

A detailed examination of LN behavior is available [88] for the blocked alanine model, the proteins BPTI and lysozyme, and a large water system, compared to reference Langevin trajectories, in terms of energetic, geometric, and dynamic behavior. The middle timestep in LN can be considered an adjustable quantity (when force splitting is used), whose value does not significantly affect performance but does affect accuracy with respect to the reference trajectories. For example, we have used Atm = 3 fs for the proteins in vacuum, but 1 fs for the water system, where librational motions are rapid.  [c.253]

In Tables 2 and 3 we show the error percentages of the LN energy components (and kinetic temperature) with respect to the explicit Langevin trajectories at At = 0.5 fs for BPTI and lysozyme simulations. The Reference column shows energy means and variances for the explicit trajectory (produced by the BBK scheme), and the LN columns (each corresponding to a different fe2 value, as indicated in the heading) show the percentage error of each entry (mean energy component and associated variance) with respect to the reference values. Here, Atm — 3 fs, so the LN variants shown (fe2 = 1, 3, 6, 12, 24, 48, and 96) correspond to outer timesteps At of 3, 9, 18, 36, 72, 144, and 288 fs, respectively.  [c.253]

The errors in the variance values (reflecting the fluctuations about the means) are larger for the total energy, variance errors can be as large as 7% for large 2 (the potential energy is the source rather than the kinetic energy) most other entries for energy components are less than 3%, except for two van der Waals values (LN 96 for BPTI and LN 3 for lysozyme) and all electrostatic entries. Note, however, that for the electrostatic energy the variance of the reference trajectory is a very small percentage of the mean value, namely 1% for BPTI. Thus, for example, the LN 96 variance (worst case for BPTI) for the electrostatic energy is still 1% of the reference energy mean although the value in the table is 33% (indicating an absolute energy variance of 16x 1.33 kcal/mol.). Thus, the values shown in Tables 2 and 3 still reflect a satisfactory agreement between LN trajectories and small-timestep analogs of the same Langevin equation. See [88] for many other examples of thermodynamic and geometric agreement.  [c.254]

Table 3. Percentage error for LN compared to reference Langevin trajectories (at 0.5 fs) for energy means and associated variances for lysozyme over 60 ps at 7 = 20 ps At = 0.5 fs, Atm = 3 fs, and At = k Atm, where k2 ranges from 1 for LN 1 to 96 for LN 96. Table 3. Percentage error for LN compared to reference Langevin trajectories (at 0.5 fs) for energy means and associated variances for lysozyme over 60 ps at 7 = 20 ps At = 0.5 fs, Atm = 3 fs, and At = k Atm, where k2 ranges from 1 for LN 1 to 96 for LN 96.
Another view of this theme was our analysis of spectral densities. A comparison of LN spectral densities, as computed for BPTI and lysozyme from cosine Fourier transforms of the velocity autocorrelation functions, revealed excellent agreement between LN and the explicit Langevin trajectories (see Fig, 5 in [88]). Here we only compare the spectral densities for different 7 Fig. 8 shows that the Langevin patterns become closer to the Verlet densities (7 = 0) as 7 in the Langevin integrator (be it BBK or LN) is decreased.  [c.255]

Finally, we show in Fig. 11 the speedup of LN at increasing outer timesteps for BPTI, lysozyme, and the large water droplet (with all nonbonded interactions included). We can see speedups exceeding an order of magnitude, reaching an asymptotic value at fairly small k. This suggests that the best compromise between efficiency and accuracy in LN is a moderate value of fe2-The asymptotic limit (analyzed in [88]) can be explained by the increasing cost of the medium forces. Note that in LN 3 for lysozyme, evaluation of the medium forces consumes 32% of the total CPU time (53% for slow forces). In LN 48, this value doubles, though the slow-force work is reduced to only 6% of the total time.  [c.255]

Fig. 11. The Speedup of LN at increasing outer timesteps for BPTI (2712 variables), lysozyme (6090 variables), and a large water system (without nonbonded cutoffs 37179 variables). For lysozyme, the CPU distribution among the fast, medium, and slow forces is shown for LN 3, 24, and 48. Fig. 11. The Speedup of LN at increasing outer timesteps for BPTI (2712 variables), lysozyme (6090 variables), and a large water system (without nonbonded cutoffs 37179 variables). For lysozyme, the CPU distribution among the fast, medium, and slow forces is shown for LN 3, 24, and 48.
B. R. Brooks and M. Karplus. Normal modes for specific motions of macromolecules Application to the hinge-bending mode of lysozyme. Proc. Natl. Acad. Sci. USA, 82 4995-4999, 1985.  [c.261]

Langevin dynamics simulations can be used to study the same kinds of problems as molecular dynamics time dependent properties of solvated systems at non-zero temperatures. Because of the implicit treatment of the solvent, this method is particularly well-suited for studying large molecules in solution. It is possible to decouple the time scales of molecular motion and focus on just the slow modes associated with conformational changes, for example, or to follow the rapid bond stretching motions leading to chemical reaction, while incorporating the influence of molecular collisions. Langevin dynamics has been use to study solvent effects on the structural dynamics of the active site of the enzyme lysozyme, conformational equilibria and the dynamics of conformational transitions in liquid alkanes, and temperature effects on a system of interacting quantum harmonic oscillators.  [c.18]

Lysozyme crystals Lys-plasminogen Lyssavirus  [c.582]

An ESI ion source produces multiply charged ions from biomolecules with high sensitivity. The analyte solution is sprayed at atmospheric pressure from a needle floated at a few kV above ground potential, and sampling cones select the center of the spray to enter the mass spectrometer via a differentially pumped transfer region. The resulting spectra contain a series of multiply charged ions each having one charge more than the next highest mass ion, and because a mass spectrometer measures the mass-to-charge ratio of an ion, ESI produces ions from large molecules which can be analyzed by such mass spectrometers as quadmpoles and ion traps. Figure 9b, an electrospray spectmm of lysozyme, shows that the most abundant ion in this case is the +9 charge state. Analysis conditions such as the pH of the analyte solution influence which charge state is the most abundant. For bovine albuinin which has a molecular mass of 66,625, the ESI mass spectmm typically contains ions having between 20 and 45 charges, ie, m/ of 3331—1481. The mass of the analyte may be calculated using the following formula  [c.547]

Protein Stability. Because it is generally accepted that the hydrophobic effect is the principal force in stabilizing globular proteins, amino acids which increase the bulk of buried hydrophobic surface area (packing density) should increase the stabihty of the protein. Many studies have been performed on the role of cavities in T4 lysozyme. Using natural amino acid replacements, some mutations designed to increase protein stabihty by filling the largest hydrophobic cavities had a slight destabilizing effect, owing to dismptive interactions with neighboring residues and the adoption of unfavorable dihedral angles (95). In contrast, the unnatural amino acids, A,A-2-amino-4-methylhexanoic acid and A-2-amino-3-cyclopentylpropanoic acid, designed to fill the cavity with minimal strain, increased the thermal stabihty of the enzyme (96). Other studies, using unnatural amino acids have probed the importance of H-bonding, and P-branching residues in the stabilization of a-hehces (93,97).  [c.206]

Abstract. Protein-ligand interactions control a majority of cellular processes and are the basis of many drug therapies. First, this paper summarizes experimental approaches used to characterize the interactions between proteins and small molecules equilibrium measurement of binding constant and standard free energy (jf binding and the dynamic approach of ligand extraction via atomic force microscopy. Next, the paper reviews ideas about the origin of different component terms that contribute to the the stability of protein-ligand complexes. Then, theoretical approaches to studying protein-small molecule interactions are addressed, including forced extraction of ligand and perturbation methods for calculating potentials of mean force and free energies for molecular transformation. Last, these approaches are illustrated with several recent studies from our laboratory (1) binding of water in cavities inside proteins, (2) calculation of binding free energy from first principles by a new application of molecular transformation, and (3) extraction of a small ligand (xenon) from a hydrophobic cavity in mutant T4-lysozyme L99A.  [c.129]

Simulation of Small Ligands Bound in T4-lysozyme L99A  [c.137]

Our recent work on the affinity of benzene for a cavity inside the structure of T4 lysozyme mutant L99A [6] has extended this method to polyatomic molecules this is achieved by coupling the transformation to a body restraint potential which restrains not only the position but aJso the orientation of the ligand molecule in the absence of interactions with the protein i.e. all six external degrees of freedom of the ligand (with simple extension to internal degrees of freedom, if needed) are restrained, rather than the three external degrees of freedom needed for a xenon atom [14] (See also discussion by Gilson et al. [10]). In our work, the following restraint potential has been used  [c.138]

We have applied simulations to the binding of several other molecules as ligands in the cavity in T4 lysozyme mutant L99A (Table 2). No binding data were available at the time for these molecules (except benzene) we were, however, aware that binding of the noble gases had been observed, and that structure determination by x-ray crystallography was in progress. The computed binding free energies agree well with observations that binding is observed at 1 atm pressure of xenon (concentration 0.0044 M), but that higher pressures are needed to observe binding of krypton and argon [30]. The crystallographic structures showed that two atoms of each noble gas were bound in the cavity, something the simulations had not taken into account. Cyclohexane is not expected to bind inside the cavity, and its binding also has not been reported the high protein-ligand energy in the equilibrated complex indicates that the puckered cyclohexane ring is too bulky for the cavity. The water-protein energy in a complex with a water molecule in the cavity is well above the threshold that was established in our study of buried water molecules, and observation of a water molecule bound inside this apolar cavity is not to be expected. In fact, after a 1 ps simulation, the water molecule escaped from the cavity into the solution.  [c.140]

Fig. 2. Work performed to extract xenon from T4 lysozyme L99A in 27 independent simulations of 100 ps each. Fig. 2. Work performed to extract xenon from T4 lysozyme L99A in 27 independent simulations of 100 ps each.
Fig. 3. Work required to extract xenon from T4 lysozyme L99A. Each value is a moan over several independent simulations. Fig. 3. Work required to extract xenon from T4 lysozyme L99A. Each value is a moan over several independent simulations.
Mann, G., Prins, J., Hermans, J. Energetics of forced extraction of ligand Simulation studies of Xe in mutant T4 lysozyme as a simple test system. Bioohys. J., in preparation (1998)  [c.147]

The presented algorithm was applied to 4 proteins (lysozyme, ribonuclease A, ovomucid and bovine pancreatic trypsin inhibitor) containing 51 titratable residues with experimentally known pKaS [32, 33]. Fig. 2 shows the correlation between the experimental and calculated pKaS. The linear correlation coefficient is r = 0.952 the slope of the line is A = 1.028 and the intercept is B = -0.104. This shows that the overall agreement between the experimental and predicted pKaS is good.  [c.188]

The small CPU percentages for the sparse Hessian evaluation and the linearization in LN as described above also imply that the majority of the work comes from gradient computations. Indeed, the percentage of CPU spent on gradient computations is about 80% for lysozyme and 99% for a large water droplet with more than 12,000 atoms (91% for this water system when nonbonded cutoffs at 12 A are enforced) [88]. This suggests that additional force splitting, as introduced by Street and coworkers in the 1970s [11] and developed further by Berne and colleagues [70, 13, 16, 17], can yield further speedups. Modern symplectic versions of these MTS methods were pioneered by Schulten and co-workers who developed the first parallel machine for MD computations [14] and independently by Berne, Tuckerman, Martyna [90] and later co-workers. Typically, the force splitting is extended into three classes fast bonded interactions, local nonbonded interactions, and nonlocal interactions. The splitting of the nonbonded interaction into short and long-range parts can be defined by a spherical range and accomplished using a smooth switching function [12, 88].  [c.252]

The visuahzation of hundreds or thousands of connected atoms, which are found in biological macromolecules, is no longer reasonable with the molecular models described above because too much detail would be shown. First of aU the models become vague if there are more than a few himdied atoms. This problem can be solved with some simplified models, which serve primarily to represent the secondary structure of the protein or nucleic acid backbone [201]. (Compare the balls and sticks model (Figure 2-124a) and the backbone representation (Figure 2-124b) of lysozyme.)  [c.133]

Figure 2-124. The most common molecular graphic representations of biological molecules (lysozyme) a) balls and sticks b) backbone c) cartoon (including the cylinder, ribbon, and tube model) and of inorganic molecules (YBajCujO , d) polyhedral (left) and the same molecule with balls and sticks (right), Figure 2-124. The most common molecular graphic representations of biological molecules (lysozyme) a) balls and sticks b) backbone c) cartoon (including the cylinder, ribbon, and tube model) and of inorganic molecules (YBajCujO , d) polyhedral (left) and the same molecule with balls and sticks (right),
Weber, P. L. Buck, D. R. Capillary Electrophoresis A Past and Simple Method for the Determination of the Amino Acid Composition of Proteins, /. Chem. Educ. 1994, 71, 609-612. This experiment describes a method for determining the amino acid composition of cyctochrome c and lysozyme. The proteins are hydrolyzed in acid, and an internal standard of a-aminoadipic acid is added. Derivatization with naphthalene-2,3-dicarboxaldehyde gives derivatives that absorb at 420 nm. Separation is by MEKC using a buffer solution of 50 mM SDS in 20 mM sodium borate.  [c.614]

Fig. 13. Preferential iateraction parameter vs lyotropic number for lysozyme on (° ) bovine semm albumin and ( ) Toyopead. Fig. 13. Preferential iateraction parameter vs lyotropic number for lysozyme on (° ) bovine semm albumin and ( ) Toyopead.
Fig. 14. Chromatographic retention of 20 )J.L of a 3 mg/mL solution of lysozyme on Toyopead HW-65S using a 50 cm x 8 min ID column in 1.3 M ammonium salt, 20 mAf Tris mobile phase at 1 ml./min for A, NH I B, NH Cl C, NH OOCCH and D, (NH 2 SO. Fig. 14. Chromatographic retention of 20 )J.L of a 3 mg/mL solution of lysozyme on Toyopead HW-65S using a 50 cm x 8 min ID column in 1.3 M ammonium salt, 20 mAf Tris mobile phase at 1 ml./min for A, NH I B, NH Cl C, NH OOCCH and D, (NH 2 SO.
Food. Foams are common to a wide variety of food products. Whipped cream and meringue are essentially foams, and ice cream is comprised of a large amount of foam. These foams are stabilized by proteins the two most important are egg white and milk proteins. For food products, it is desirable not only to achieve good foaming properties, but also to form stable foams (41—44). The ease with which foams are formed depends on the capacity of the proteins to rapidly adsorb onto the interface. The stabiHty of the foams depends on the abiHty of the proteins to form an elastic membrane at the interface, which both prevents bubble coalescence and is sufficiently impermeable to reduce gas diffusion. One of the best food-foaming agents is egg white or egg albumen. It consists of a mixture of different proteins, each serving a particular function (45). GlobuHns are the most surface-active agents, leading to good foamabiHty drainage is retarded by the high viscosity caused by globuHns and ovomucoids the film strength is enhanced by surface complexes formed between lysozymes and ovomucins. Upon heating, thermal denaturation of ovalbumin and conalbumin results in a more permanent foam stmcture, leading to its widespread use in baked products. Ice cream is also a type of foam possessing varying amounts of air bubbles incorporated during an aeration step in the processing (46). These bubbles are initially stabilized by milk proteins, primarily P-casein, a-lactalbumin, and P-lactoglobuHn (47). Further stabilization occurs due to the adsorption of fat globules on the interface.  [c.431]

Many enzymes have been the subject of protein engineering studies, including several that are important in medicine and industry, eg, lysozyme, trypsin, and cytochrome P450. SubtiHsin, a bacterial serine protease used in detergents, foods, and the manufacture of leather goods, has been particularly well studied (68). This emphasis is in part owing to the wealth of stmctural and mechanistic information that is available for this enzyme.  [c.203]


See pages that mention the term Lysozyme : [c.244]    [c.1708]    [c.41]    [c.213]    [c.654]    [c.582]    [c.582]    [c.999]    [c.56]    [c.439]    [c.545]    [c.287]   
Computational biochemistry and biophysics (2001) -- [ c.2 , c.243 , c.372 , c.384 ]

Introduction to protein structure (1999) -- [ c.0 ]