Protonation trajectories

Despite the trigonal anomeric center and the consequential 4H3 conformation, both inhibitors are too weak to constitute transition-state analogues, making them good examples among glycosidases as protonation trajectory-selective probes for in-plane... 

Protonation trajectories, (a) Protonation perpendicuiar to the piane of the ring, (b) a/7f/-protonation, (c) syn-protonation, (d) iaterai protonation moves the fissiie C-0 bond into a pseudoaxiai position (after [69])... 

Although one can write a canonical mechanism for retaining O-glycosidases, there are departures from this mechanism in acid-catalytic machinery and the nature of the nucleophile (for some families, not the carboxylate shown). In Table 5.4 are set out the nature of the catalytic groups, the protonation trajectory and the conformations of substrate and glycosyl enzyme, where at least two of these are known. 

Figure 5.32 Canonical mechanism for a retaining glycosidase or transglycosylase Whether the substrates are pyranosidases or furanosidases, whether the leaving group is axial or equatorial and whether the protonation trajectory is syn or anti depend on the enzyme. If R = R, then the principle of microscopic reversibility requires transition states 1 and 2 to be identical. More generally, the group which acts as a general acid in the first step must act as a general base in the second.

Table 5.4 Substrate stereochemistry, acid/base groups, nucleophiles, protonation trajectory and substrate and glycosyl-enzyme intermediate conformations, where known.

Fig. 6. Syn (a) and anti (b) protonation trajectories for 8-glycosidases. The substrate is drawn in a distorted skew-boat form, as observed in enz5mie-substrate complexes (c Fig. 7)...

Collision-induced dissociation mass spectrum of tire proton-bound dimer of isopropanol [(CH2)2CHOH]2H. The mJz 121 ions were first isolated in the trap, followed by resonant excitation of their trajectories to produce CID. Fragment ions include water loss mJz 103), loss of isopropanol mJz 61) and loss of 42 anui mJz 79). (b) Ion-molecule reactions in an ion trap. In this example the mJz 103 ion was first isolated and then resonantly excited in the trap. Endothennic reaction with water inside the trap produces the proton-bound cluster at mJz 121, while CID produces the fragment with mJz 61. 

By using this approach, it is possible to calculate vibrational state-selected cross-sections from minimal END trajectories obtained with a classical description of the nuclei. We have studied vibrationally excited H2(v) molecules produced in collisions with 30-eV protons [42,43]. The relevant experiments were performed by Toennies et al. [46] with comparisons to theoretical studies using the trajectory surface hopping model [11,47] fTSHM). This system has also stimulated a quantum mechanical study [48] using diatomics-in-molecule (DIM) surfaces [49] and invoicing the infinite-onler sudden approximation (lOSA). 

In molecular mechanics and molecular dynamics studies of proteins, assig-ment of standard, non-dynamical ionization states of protein titratable groups is a common practice. This assumption seems to be well justified because proton exchange times between protein and solution usually far exceed the time range of the MD simulations. We investigated to what extent the assumed protonation state of a protein influences its molecular dynamics trajectory, and how often our titration algorithm predicted ionization states identical to those imposed on the groups, when applied to a set of structures derived from a molecular dynamics trajectory [34]. As a model we took the bovine... 

Another principal difficulty is that the precise effect of local dynamics on the NOE intensity cannot be determined from the data. The dynamic correction factor [85] describes the ratio of the effects of distance and angular fluctuations. Theoretical studies based on NOE intensities extracted from molecular dynamics trajectories [86,87] are helpful to understand the detailed relationship between NMR parameters and local dynamics and may lead to structure-dependent corrections. In an implicit way, an estimate of the dynamic correction factor has been used in an ensemble relaxation matrix refinement by including order parameters for proton-proton vectors derived from molecular dynamics calculations [72]. One remaining challenge is to incorporate data describing the local dynamics of the molecule directly into the refinement, in such a way that an order parameter calculated from the calculated ensemble is similar to the measured order parameter. 

A Warshel. Dynamics of reactions m polar solvents. Semiclassical trajectory studies of electron-transfer and proton-transfer reactions. J Phys Chem 86 2218-2224, 1982. 

On the other hand, it is clear that in the classical regime, T> (T i is the crossover temperature for stepwise transfer), the transition should be step-wise and occur through one of the saddle points. Therefore, there should exist another characteristic temperature. r 2> above which there exist two other two-dimensional tunneling paths with smaller action than that of the one-dimensional instanton. It is these trajectories that collapse to the saddle points atlT = T i. The existence of the second crossover temperature, 7, 2, for two-proton transfer has been noted by Dakhnovskii and Semenov [1989]. 

The bifurcational diagram (fig. 44) shows how the (Qo,li) plane breaks up into domains of different behavior of the instanton. In the Arrhenius region at T> classical transitions take place throughout both saddle points. When T < 7 2 the extremal trajectory is a one-dimensional instanton, which crosses the maximum barrier point, Q = q = 0. Domains (i) and (iii) are separated by domain (ii), where quantum two-dimensional motion occurs. The crossover temperatures, Tci and J c2> depend on AV. When AV Vq domain (ii) is narrow (Tci — 7 2), so that in the classical regime the transfer is stepwise, while the quantum motion is a two-proton concerted transfer. This is the case when the tunneling path differs from the classical one. The concerted transfer changes into the two-dimensional motion at the critical value of parameter That is, when... 

One after the other, step through (or animate) the sequence of structures depicting the SN2 and proton transfer reactions shown above. Compare the two. From what direction does cyanide approach the hydrogen in HCl From the same side as Cl ( frontside ), or from the other side ( backside ) Does the Sn2 reaction follow a similar trajectory ... 

FIGURE 5.8. A downhill trajectory for the proton transfer step in the catalytic reaction of trypsin. The trajectory moves on the actual ground state potential, from the top of the barrier to the relaxed enzyme-substrate complex. 1, 2, and 3 designate different points along the trajectory, whose respective configurations are depicted in the upper part of the figure. The time reversal of this trajectory corresponds to a very rare fluctuation that leads to a proton transfer from Ser 195 to His 57. 

Reactive trajectories, 43-44,45, 88,90-92,215 downhill trajectories, 90,91 velocity of, 90 Relaxation processes, 122 Relaxation times, 122 Reorganization energy, 92,227 Resonance integral, 10 Resonance structures, 58,143 for amide hydrolysis, 174,175 covalent bonding arrangement for, 84 for Cys-His proton transfer in papain, 141 for general acid catalysis, 160,161 for phosphodiester hydrolysis, 191-195,... 

Figure 7-2. Properties of CAII active site in the COHH state (zinc-bound hydroxide and protonated His 64). (a) Superposition of a few key residues from two stochastic boundary SCC-DFTB/MM simulations with the X-ray structure [87] (colored based on atom-types) the two sets of simulations did not have any cut-off for the electrostatic interactions between SCC-DFTB and MM atoms but used different treatments for the electrostatic interactions among MM atoms group-based extended electrostatics (in yellow) and atom-based force-shift cut-off (in green). Extended electrostatics simulations sampled configurations with the protonated His 64 too close to the zinc moiety while force-shift simulations consistently sampled the out configuration of His 64 in multiple trajectories, (b) Statistics for productive water-bridges (only from two and four shown here) between the zinc bound water and His 64 with different electrostatics protocols...

We consider the example of a particular trajectory of the H+ + 7/2(0,0) —> //2(v,/j + 77 at an energy of 1.2 eV in the center-of-mass frame. By using an atomic orbital basis and a representation of the electronic state of the system in terms of a Thouless determinant and the protons as classical particles, the leading term of the electronic state of the reactants is... 

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