Infrequent events

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)... 

Hammes-Schiffer S and Tully J C 1995 Nonadiabatic transition state theory and multiple potential energy surfaces molecular dynamics of infrequent events J. Chem. Phys. 103 8528... 

One of the basic problems in molecular dynamics is how to sample infrequent events. Typically a reaction must pass over a barrier, and effort would be wasted if many trajectories are run that do not reach the reactant channel. 

Standard alkylating and cross-linking agents such as dimethylsulfate or TV-mustards, respectively, have only one opportunity to partition between various nucleophiles since their reactions are irreversible. In contrast, QMs have the potential to partition between nucleophiles multiple times as long as the resulting adducts are formed reversibly. Continual capture and release of QMs consequently can extend their effective lifetime almost indefinitely and is ultimately limited by only the competitiveness of possible irreversible reactions. For DNA, the strongest nucleophiles act reversibly so terminal quenching remains an infrequent event. 

Because there are two positive terms in the denominator of equation 4.2.85 (either of which may be associated with the dominant termination process), this equation leads to two explosion limits. At very low pressures the mean free path of the molecules in the reactor is quite long, and the radical termination processes occur primarily on the surfaces of the reaction vessel. Under these conditions gas phase collisions leading to chain breaking are relatively infrequent events, and fst fgt. Steady-state reaction conditions can prevail under these conditions if fst > fb(a — 1). 

Voter, A.F., Hyperdynamics Accelerated molecular dynamics of infrequent events, Phys. Rev. Lett. 1997, 78, 3908-3911... 

Voter, A.F., A method for accelerating the molecular dynamics simulation of infrequent events, 7. Chem. Phys. 1997,106, 4665-4677... 

Keywords infrequent events transition-state theory accelerated dynamics hyperdynamics parallel-replica dynamics temperature-accelerated dynamics molecular dynamics bond-boost hyperdynamics parallel-accelerated dynamics Cu(100)... 

There may be particular difficulties in characterizing the tails of distributions, because the distribution tails relate to relatively infrequent events. 

Tardive dyskinesia is also frequently mentioned as a reason to minimize exposure, but this condition usually develops after more chronic exposure. The relationship between TD and prior neuroleptic dosing is uncertain at this time, and the authors are not aware of any studies indicating that an acute, time-limited use of higher neuroleptic doses increases the prevalence of this disorder (338). Fortunately, the occurrence of NMS is an infrequent event (less than 1.5%), with no occurrences noted in the 676 cases reviewed by Dubin. In the discussion on adverse effects (later in this chapter), however, we note a higher incidence has been found by others during rapid dose increases. 

The ability to innovate also involves learning from past mistakes, not just one s own. Mistakes and errors in practices can be both costly and dangerous but can be prevented from occurring successively if their causes are determined. This can be difficult because a near-miss scenario can be seen either as an infrequent event or as an averted disaster. The first reaction to this is usually to continue without changing current practices, allowing for similar mistakes to occur. Learning requires all levels of an organization to participate and create channels of communication to innovate effectively, as the inability to share experience denies new opportunities [13,29-40]. 

Transition state theory (TST) (4) is a well-known method used to calculate the kinetics of infrequent events. The rate constant of the process of interest may be factored into two terms, a TST rate constant based on a knowledge of an equilibrium phase space distribution of the system, and a dynamical correction factor (close to unity) used to correct for errors in the TST rate constant. The correction factor can be evaluated from dynamical information obtained over a short time scale. 

Molecular Dynamics and Transition State Theory The Simulation of Infrequent Events... 

Table I. outlines the steps for finding the bottleneck, evaluating the rate constant, and generating typical trajectories for infrequent events.

Radical B may of course result also from attack by radicals from AIBN. In that event or in the event of transfer from the polymer radical to solvent, a new polymer chain will be started by B and this chain will have no AIBN fragment at that end. Coupling of two B radicals is assumed to be a very infrequent event. Transfer to monomer, to polymer or to initiator are infrequent also. The transfer constants are approximately 1 x 10 5 for transfer to monomer at 25° (108) and 2.7 x 1CL4 for transfer to DMF at 50° (135). Srinivasan and Santappa (126) suggest that the values for DMF are 1.0 x 10-4 at 50° and 2.4 x 10-4 at 60°, although this requires an unexpectedly high activation energy of 18 kcal per mole for transfer. Hydrated DMF appears to be relatively inert toward transfer (84). 

Among the methods utilizing the TST, the parallel replica method is the simplest and most accurate dynamics techniques, because the only assumption for the method is that of infrequent events obeying first-order kinetics (exponential decay). In practice, replicated MD simulations are started in a particular basin state in search for a transition to an adjacent basin state on M non-correlated processors. Whenever a transition is detected on any processor, the... 

Deviations should be an infrequent event. A high rate of deviations is indicative of an uncontrolled process that has not been adequately validated. Quality assurance be aware of the overall rate of deviations to batch records and take appropriate actions as necessary. 

For most of the other monoclonal antibodies, species cross-reactivity has been limited to nonhuman primates. For these molecules the need to conduct reproductive and developmental studies has to be carefully considered on a case-by-case basis. S5A states that nonhuman primates are best used when the objective of the study is to characterize a relatively certain reproductive toxicant, rather than detect a hazard. The nonhuman primate reproductive toxicity studies are not powered to detect infrequent events. 

E. K. Grimmelmann, J. C. Tully, and E. Helfand, Molecular Dynamics of Infrequent Events Thermal Desorption of Xenon from a Platinum Surface, J. Chem. Phys., 74 (1981) 5300. 

The lac repressor is a tetramer that can simultaneously bind to two operators to form a DNA loop and dissociates from DNA under a high inducer concentration [38] (Fig. 22.8A). Under low inducer concentrations (Fig. 22.8B), the repressor cannot be pulled off the DNA by the inducer. Rather, spontaneously, partial dissociations of the repressor result in transcription of one mRNA and a small burst of proteins, as seen in Fig. 22.4B. Flowever, infrequent events of complete dissociation of the repressor result in large bursts of permease expression that trigger induction of the lac operon... 

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