Restraining Protocol

In many cases, it is also helpful to have the path repel itself so that the transition pathway is self-avoiding. An acmal dynamic trajectory may oscillate about a minimum energy configuration prior to an activated transition. In the computed restrained, selfavoiding path, there will be no clusters of intermediates isolated in potential energy minima and no loops or redundant segments. The self-avoidance restraint reduces the wasted effort in the search for a characteristic reaction pathway. The constraints and restraints are essential components of the computational protocol. 

In a typical free NOESY experiment of a molecule in the absence of any interacting protein, cross-peak volumes are interpreted in terms of a set of interproton distances r that can be used as distance restraints in structure determination procedures, like restrained simulated annealing protocols [44], In a tr-NOESY, i.e. a NOESY measured under exchange-transferred conditions in the presence of a protein - i.e., an excess of soluble ligand is in fast exchange equilibrium with a smaller amount of protein-bound ligand -, these r reflect the interproton distances of the ligand in the bound... 

Since this early work, experience has accumulated with restrained MD and some points can be made with respect to the effects of restrained MD and simulation protocol. First, if the starting structures have already been very highly refined with respect to distances, and if the distance restraints are very numerous and accurate, then the restrained MD protocol will not make much difference. If the starting structures are less well refined or the restraints less numerous, then restrained MD will be important, as will the choice of protocol. 

Figure 8. Illustration of the use of the umbrella potential. The umbrella potential (dashed line) restrains the system to sample a defined region of the phase space (grey region). In the MCTI or MSTP protocol multiple simulations are performed with an umbrella potential that evolves with the coupling parameter X and allows a gradual sampling of the coordinate of interest.

As for global participation, commitments by the South in the Kyoto Protocol are conspicuous by their absence. Throughout the negotiations, developing nations have resisted discussing even voluntary measures to restrain their emissions. 

---