Sampling the equilibrium kinetic network of Trp-cage in explicit solvent.
We employed the single replica multiple state transition interface sampling (MSTIS) approach to sample the kinetic (un)folding network of Trp-cage mini-protein in explicit water. Cluster analysis yielded 14 important metastable states in the network. The MSTIS simulation thus resulted in a full 14 × 14 rate matrix. Analysis of the kinetic rate matrix indicates the presence of a near native intermediate state characterized by a fully formed alpha helix, a slightly disordered proline tail, a broken salt-bridge, and a rotated arginine residue. This intermediate was also found in recent IR experiments. Moreover, the predicted rate constants and timescales are in agreement with previous experiments and simulations.
Van't Hoff Institute for Molecular Sciences, University of Amsterdam, PO Box 94157, 1090 GD Amsterdam, The Netherlands.
Weina
W
Du
Van't Hoff Institute for Molecular Sciences, University of Amsterdam, PO Box 94157, 1090 GD Amsterdam, The Netherlands.
Peter G
PG
Bolhuis
D001665:Binding Sites; D003198:Computer Simulation; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics
D010455:Peptides; D012997:Solvents; C508725:Trp-cage peptide