Coarsely resolved topography along protein folding pathways

摘要: The kinetic data from the coarse representation of polypeptide torsional dynamics described in preceding paper [Fernandez and Berry, J. Chem. Phys. 112, 5212 (2000), paper] is inverted by using detailed balance to obtain a topographic description potential-energy surface (PES) along dominant folding pathway bovine pancreatic trypsin inhibitor (BPTI). topography represented as sequence minima effective saddle points. displays an overall monotonic decrease energy with large number staircaselike steps, clear signature good structure-seeker. diversity availability alternative pathways analyzed terms Shannon entropy σ(t) associated time-dependent probability distribution over ensemble contact patterns. Several stages process are evident. Initially misfolded states form dismantle revealing no definite pattern exhibiting high entropy. Passage down staircase steps then leads formation nativelike intermediate, for which much lower fairly constant. Finally, structure intermediate refined produce native state BPTI. We also examine how different levels tolerance mismatches side chain contacts influence kinetics, pathway, This analysis yields upper bounds frustration required expeditious robust