Transition state ensemble structures

The path ensemble, as created by the transition path sampling methodology, is a statistically representative collection of trajectories leading from a reactant region to a product region. Further analysis of this ensemble of pathways is necessary to obtain rate constants, reaction mechanisms, reaction coordinates, transition state structures etc. In this section we will describe how to analyze the path ensemble by determining transition state ensembles, and how to test proposed reaction coordinates using committor distributions. 

Clement C, Nymeyer H, Onuchic JN. 2000. Topological and energetic factors What determines the structural details of the transition state ensemble and en-route intermediates for protein folding An investigation for small globular proteins. Journal of Molecular Biology 298 937. 

Energetic Factors What Determines the Structural Details of the Transition State Ensemble and en-route Intermediates for Protein Folding An Investigation for Small Globular Proteins. 

Determination of the Structures of Distinct Transition State Ensembles for a Beta-sheet Peptide with Parallel Folding Pathways. 

Loop Restricts the Structural Heterogeneity of the Transition State Ensemble in SH3 Domains. 

In connecting these ideas with earlier phenomenological models, it is not obvious how to reconcile the dependence of the rate on the structure with a nucleation mechanism, as in Ref. 50. The statistical relationship suggests that the transition state contains a considerable amount of native structure, while a nucleus, in the classic sense of the word, is a small part of the structure. However, it could be that a limited number of native contacts (i.e., those in the nucleus) are sufficient to confine the transition state ensemble to a native-like fold. This idea is supported by a recent analysis of the folding transition state of acylphosphatase in which key residues, as determined by a < ) value analysis, play a critical role [56]. 

Therefore, X can be conveniently used to monitor the progress of the chemical reaction in the solvent reaetion coordinate. Clearly, there is no single reactant structure that defines the transition state, rather, an ensemble of transition states will be obtained from the simulation, which may contain solute geometries... 

Figure 19.18 Energy level diagrams for protein folding. The conformations of the denatured state ensemble U and Dphys are drawn, for convenience, as stacked. Those denatured conformations that have some elements of native structure could be drawn more accurately as being on the reaction pathway and closer to the transition state.

The distinction is sometimes made between a transition state and a transition structure [4]. Strictly speaking, a transition state is a thermodynamic concept, the species an ensemble of which are in a kind of equilibrium with the reactants in Eyring s2 transition-state theory [5]. Since equilibrium constants are determined by free energy differences, the transition structure, within the strict use of the term, is a free energy maximum along the reaction coordinate (in so far as a single species can... 

It is recommended to carry out a set of SV measurements of the unfolded and the folded state ensembles as a function of RNA concentration as described earlier before collecting the data points for the entire equilibrium transition. The shape of the apparent sedimentation coefficient distribution curves (discussed in Section 5) derived from such measurements, indicate whether the initial and the final states are conformationally homogeneous. Appearance of more than one peak in such distributions would indicate the existence of distinct structural states with different hydrodynamic properties. 

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