Fig 1.
Folding pathway of GB1 (PDB ID:1pgb) and LB1 (PDB ID:1hz5).
(a) and (d) are the native structure of GB1 and LB1. (b) and (e) are the folding pathway of GB1 and LB1 including intermediate states. (c) and (f) are the contact orders of the intermediate states. Residue contact order values are normalized and represented on the structure as color.
Fig 2.
Folding pathways of eSH3 (PDB ID:1shg) and cSH3 (PDB ID:4jz4).
(a) and (d) respectively their native structures. (b) and (e) are folding pathway including the intermediate states. (c) and (f) are contact order of intermediate states.
Fig 3.
Folding pathway of LysM (PDB ID: 1e0g).
(a) is the native structure of the LysM protein. (b) is the contact order of the intermediate states. (c) is the folding pathway including the intermediate states and their residue contact order.
Fig 4.
Folding pathways of four unexperimented proteins.
Folding pathways include intermediate state structure information and normalized residue contact order. The color annotation of residue contact order is consistent with the intermediate state in Fig 1.
Fig 5.
Schematic diagram of folding pathway prediction based on conformational sampling.
The yellow structures are sampling states and cyan structures are seed states. The dotted arrows indicate the implicit transition between intermediate states. Sampling states are obtained by the large-scale conformational sampling. The seed states and their transition tendency are inferred by the resampling algorithm.
Fig 6.
(A) Seed generation. Sampling of large-scale conformational space by input sequences. Cluster and output the seed states. (B) Transition probability exploration. The seed states in this stage consists of the seeds obtained in stage A and the input native structure. (C) Folding pathway inference. The folding pathway starts from the unfolded state and passes through several intermediate states to a near-native state (N’), which is the closest conformation to native during sampling.
Fig 7.
Schematic of the modified energy landscape.
After modification, the energy basin is raised and the energy barrier is lowered. And the relatively smooth energy landscape makes transitions between states easy.