Reaction path conjugate peak refinement

Figure 5,30 reprinted from Chemical Physical Letters, 194, Fischer S and M Karplus. Conjugate Peak Refinement An Algorithm for Finding Reaction Paths and Accurate Transition States in Systems with Many Degrees of Freedom. 252-261, 1992, with permission from Elsevier Science. 

An alternative means of calculating reaction pathways is employed in so-called global methods. These methods treat the entire path as a succession of points [71] which are found simultaneously. Methods of this type (for example the conjugate peak refinement algorithm [72], available in the TRAVEL module of CHARMM, which has the advantage of requiring only first derivatives of the energy) have been used to determine reaction paths in a number of proteins [4, 73]. 

Using the conjugate peak refinement method, Fischer et al. [20a] calculated the reaction path of the motion of the biological water molecules. They also compared the computed transition state and activation energy to those in ice. Their calculation shows that the motion of the water molecules, buried in the proteins, involves exchange of two water hydrogen atoms and involves two successive rotations around orthogonal axes. 

S. Fischer and M. Karpins. Conjugate peak refinement An algorithm for finding reaction paths and accurate transition states in systems with many degrees of freedom. Chem. Phys. Lett. 194,1992, 252-261. 

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