Predicting folding rates from umbrella sampled data.

HOFFMAN, RMB; BERGER A; CRAIG PO; KOMIVES EA; SCHAFER N; WOLYNES P

San Diego, California, USA.

Congreso; Biophysical Society 56th Annual Meeting,; 2012

Hoffman R, Berger A, Craig PO, Komives E, Schafer N, Wolynes P.

The mechanistic interpretation of continuous molecular dynamics time series faces well-understood challenges, primarily obtaining a statistically significant number of folding trajectories under a sufficiently accurate force field. To avoid some of these limitations, here we use discontinuous sampling over the folding reaction coordinate (umbrella sampling) with a greatly simplified protein model (three beads per amino acid), in implicit solvent. Such approaches give thermostatistics that are consistent with a given force field, but a specific mechanism is not (rigorously) directly inferable from thermodynamic data. Here we present some strategies towards calculating kinetic observables from discontinuously sampled data. We use the concept of foldons, and the assumption of a universal, maximum folding rate, to assign folding mechanisms with explicit kinetics.