Comparison of successive transition states for folding reveals alternative early folding pathways of two homologous proteins

• DOI: 10.1073/pnas.0804774105
• Publication Date: 2008-11-26T01:14:00Z
• Authors: Nicoletta Calosci; Celestine N. Chi; Barbara Richter; Carlo Camilloni; Åke Engström; Lars Eklund; Carlo Travaglini-...; Stefano Gianni; Michele Vendruscolo; Per Jemth
• Keywords: Folding (DSP implementation); Energy landscape; Transition state; Protein superfamily; Contact order; Folding funnel

The energy landscape theory provides a general framework for describing protein folding reactions. Because large number of studies, however, have focused on two-state proteins with single well-defined pathways and without detectable intermediates, the extent to which free landscapes are shaped up by native topology at early stages process has not been fully characterized experimentally. To this end, we investigated mechanisms two homologous three-state proteins, PTP-BL PDZ2 PSD-95 PDZ3, compared late transition states their pathways. Through combination Φ value analysis molecular dynamics simulations obtained atomic-level structures these found that much more structurally similar than ones. Our findings thus reveal that, while state defines essentially in unique way folding, it leaves significant freedom events, result reflects funneling toward state.