Stochastic Dynamics and Dominant Protein Folding Pathways

Pietro Faccioli (1, 2) , Marcello Sega (3) , Francesco Pederiva (4) , Henri Orland (5)

1 Physics Department and INFN
2 Pietro Faccioli
3 Frankfurt Institute for Advanced Studies
4 Physics Department
5 Institut de Physique Theorique

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 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 a 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.

Mots clés: Physical Sciences

Pietro Faccioli, Marcello Sega, Francesco Pederiva, Henri Orland. Stochastic Dynamics and Dominant Protein Folding Pathways. Philosophical Magazine, 2008, 88 (33-35), pp.4093-4099. ⟨10.1080/14786430802609644⟩. ⟨hal-00514002⟩