Molecular dynamic simulations barrier crossing

Force a geom ctric param etcr to cross a barrier diiriti g a geoin e-try optimi/,alioTi or molecular dynamics simulation. 

Molecular dynamic simulations are very useful for solvation dynamic studies. In contrast to the difficulties described in applying numerical methods to the problems of vibrational relaxation (Section 13.6) and barrier crossing (Section 14.7), solvation dynamics is a short-time downhill process that takes place (in pure simple solvents) on timescales easily accessible to numerical work. 

Figure 11.17 Molecular dynamics simulation of the 0 + H2 OH + H exchange reaction in supercritical Ar where the atomic structure of the solvent is fully retained in the simulations. Shown are the O-H and H—H bond distances vs. time. The dense solvent cages the reactants (as well as the products). There are several tries to cross the barrier, but only the attempt at time zero is successful [adapted from Ben-Nun and Levine (1994)]. To perform such computations it is advantageous to initiate the trajectory at t = 0 at the barrier top and to integrate both forward and backward in time (Bennett, 1977).

This is a general expression for the calculation of the kinetic factor for diffusive barrier crossing. Using a Molecular Dynamics simulation one only needs to measure the change in size of the critical cluster as a function of time. The only restriction is that, during the measurement, the critical nucleus needs to fluctuate around its critical value. 

If the metadynamics method is applied to the simulation of chemical reactions in conjunction with Car-Parrinello molecular dynamics [36,40,49], the history dependent potential has to force the system to cross barriers of several tenths of kcal/mol in a very short time, usually a few picoseconds. This implies that a lot of energy is injected in the degrees of freedom associated with the collective variables. This might lead to a significant dishomogeneity in the temperature distribution of the system, and possibly to instabilities in the dynamics. 

The differences of the initial structure generation procedure will influence the quality of NMR structures, because of the initial structure dependency of the calculations. The ability to cross the potential barrier (i.e., conformational space exploration efficiency) definitely depends on the molecular dynamics conditions (typically simulation time). The conditions, however, are usually not validated, because of limitations by computational resources. The computing power required is linearly dependent on the simulation time, and thus has been a strong limitation of the calculations. Furthermore, temperature and steric repulsion weighing schedules as well as the force field will influence the structural quality. 

---