Transition-state simulation

Variational Transition State Simulations for Chemical Reactions in Solution... 

Keywords Cocaine Hydrolysis mechanism Transition-state simulation ... 

Computational Design of BChE Mutants Based on Transition State Simulations... 

The computational predictions based on the transition state simulations were followed by wet experiments [117]. The wet experiments have revealed that A199S/S287G/A328W/Y332G BChE has a 456-fold im-... 

Although experimental techniques such as X-ray crystallography, NMR, and other spectroscopic methods are critical for studying enzyme structure, they are sometimes unable to answer questions concerning detailed catalytic mechanisms. Computational approaches allow the direct assessment and characterization of the enzyme-substrate (ES) and enzyme-product (EP) complexes, as well as transient species such as metastable intermediates and transition states. Simulation also enables enzyme reaction energetics to be dissected into individual contributions. Thus, computer simulation can provide important information that is complementary to experiments. 

Table 23.1 lists the results for the activation free energies obtained for the hydrolysis of methyl formate in solution, using diffeent methods and the mechanisms described in this work. Our MD results were obtained from the free-energy curves Gr and Gts shown in Fig. 23.2, which were constructed from reactant and transition state simulations using ab initio potentials. 

Bennett C H 1977 Molecular dynamics and transition state theory the simulation of infrequent events Algorithms for Chemical Computation (ACS Symposium Series No 46) ed R E Christofferson (Washington, DC American Chemical Society)... 

At any geometry g.], the gradient vector having components d EjJd Q. provides the forces (F. = -d Ej l d 2.) along each of the coordinates Q-. These forces are used in molecular dynamics simulations which solve the Newton F = ma equations and in molecular mechanics studies which are aimed at locating those geometries where the F vector vanishes (i.e. tire stable isomers and transition states discussed above). 

In summary, a wealtli of experimental data as well as a number of sophisticated computer simulations univocally indicate that two important effects underlie the acceleration of Diels-Alder reactions in aqueous media hydrogen bonding and enforced hydrophobic interactionsIn terms of transition state theory hydrophobic hydration raises the initial state more tlian tlie transition state and hydrogen bonding interactions stabilise ftie transition state more than the initial state. The highly polarisable activated complex plays a key role in both of these effects. 

A Tropsha, J Hermans. Application of free energy simulations to the binding of a transition-state-analogue inhibitor to HIV protease. Protein Eng 51 29-34, 1992. 

In a similar way, computational chemistry simulates chemical structures and reactions numerically, based in full or in part on the fundamental laws of physics. It allows chemists to study chemical phenomena by running calculations on computers rather than by examining reactions and compounds experimentally. Some methods can be used to model not only stable molecules, but also short-lived, unstable intermediates and even transition states. In this way, they can provide information about molecules and reactions which is impossible to obtain through observation. Computational chemistry is therefore both an independent research area and a vital adjunct to experimental studies. 

Active Figure 5.5 A hypothetical transition-state structure for the first step of the reaction of ethylene with HBr. The C=C 77 bond and H-Br bond are just beginning to break, and the C-H bond is just beginning to form. Sign in afwww.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

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