Stochastic dynamics and dominant protein folding pathways

Abstract

We present the results of a recently developed theoretical framework denominated Dominant Reaction Pathways (DRP), to study thermally activated reactions in multi-dimensional systems. In particular, we focus on application to the protein folding reaction. By applying the saddle-point approximation to the stochastic path integral generated by the Langevin equation, we derive a least-action principle, which allows us to rigorously determine directly the most probable reaction pathways, bypassing the long-standing computational problems associated with the decoupling of time-scales in the problem. We show the results of number validation studies, in which the accuracy of the DRP approach was assessed, studying molecular transitions. In all cases, the DRP predictions are found to be consistent with the MD results, but extremely less computationally expensive.

Keywords:

• polymer dynamics
• protein folding
• stochastic path integrals

Notes

Note

1. Two residues are considered in contact if their distance is less than 6 A. The fraction of native-like contacts in Figure 2 is defined as the number of non-consecutive residues in contact, divided by the number of non-consecutive residues in contact in the native state.