Oral Presentation 2014 International Biophysics Congress

Dominant Reaction Pathways approach for protein folding and conformational transitions (#141)

Silvio a Beccara 1 , Pietro Faccioli 2 , Cristian Micheletti 3 , Tatjana Skrbic 3 , Roberto Covino 4
  1. Fondazione Bruno Kessler, Povo, Italy
  2. Physics, Università di Trento, Trento, Italy
  3. Statistical and Biological Physics, SISSA, Trieste, Italy
  4. Theoretical Biophysics, Max Planck Institute for Biophysics, Frankfurt, Germany

The Dominant Reaction Pathways (DRP)1  approach is a framework aimed at the efficient computation of the most probable folding pathways connecting denatured protein configurations to the native state. Its high computational efficiency enables the simulation of very slow (up to hours) transitions on large systems (hundreds of residues), with realistic atomistic force fields3 . It can also be used to predict the most probable pathways for a conformational transition between given states of macromolecules.

In my talk I will outline the basic features of the DRP method and give an account of its latest applications. I will first discuss the folding of a natively knotted protein2 . I will then describe the conformational transition of a serpin comprised of 373 residues between its active (metastable) state and its latent state3 . I will also show the importance of the detailed knowledge of the transition pathway for biomedical applications. Lastly, I will present the folding pathway of the PAI-1 serpin from a totally denatured configuration.

  1. S. a Beccara, T. Škrbić, R. Covino, Pietro Faccioli Dominant folding pathways of a WW domain, PNAS 109 (2012) 7
  2. S. a Beccara, T. Skrbic, R. Covino, C. Micheletti, P. Faccioli, Folding Pathways of a Knotted Protein with a Realistic Atomistic Force Field, PLoS Comput Biol 9(3): e1003002. doi:10.1371/journal.pcbi.1003002
  3. G. Cazzolli,F. Wang, S. a Beccara, A. Gershenson, P. Faccioli and P. L. Wintrode, Atomic-level characterization of the serpin latency transition, submitted to Science