PyRosetta Fold Trees

#What is a Fold Tree# A fold tree in PyRosetta specifies how residues in the pbd file are connected to each other. The fold tree has two main components - jump edges and peptide edges. Peptide edges specify the order of connectivity between peptides in one polymer from start to end. For example, a 100 residue protein folded from the middle out would have two edges, 50 to 1, and 50 to 100. Jump edges specify connection between residues that are not part of the peptide sequence. For example, if residue x is connected to residue y in some way such that y != x+/-1, the connection will be specified using a jump edge. This is useful for defining the connection between two separate chains for docking

#Cas9 Fold Trees# PyRosetta only allows docking between two partners using the DockMCMProtocol. It is possible to specify a fold tree to be generated manually, or using the automatic fold tree generation functions. The pdb file for 4UN3.pdb also has a default fold tree that generates with the pdb file. Automatic fold tree generation can be specified with setup_foldtree(pose, partners, Vector1([1])), where partners is a string with an '_' between the two chains to be docked. Fold Tree generated by setup_foldtrees() only distinguish based on the characters directly to either side of the underscore. I.e. partners 'AB_CD', 'AB_C', 'B_CD', 'B_C' all produce identical fold tree. This means, given the four chains present in the pdb, and that we want to dock chains B and D, there are four possible fold tree setups: Default, partners 'B_C', partners 'B_D', and a manual fold tree.

Possible fold trees: ###Default### FOLD_TREE EDGE 1 81 -1 EDGE 1 82 1 EDGE 82 1387 -1 EDGE 1 1388 2 EDGE 1388 1415 -1 EDGE 1 1416 3 EDGE 1416 1426 -1 ###B_C### FOLD_TREE EDGE 1 81 -1 EDGE 81 82 2 EDGE 82 138 -1 EDGE 138 1387 -1 EDGE 138 1416 1 EDGE 1416 1426 -1 EDGE 1416 1415 3 EDGE 1415 1388 -1 ###B_D### FOLD_TREE EDGE 1 81 -1 EDGE 81 82 3 EDGE 82 138 -1 EDGE 138 1421 1 EDGE 1421 1426 -1 EDGE 1421 1416 -1 EDGE 138 1387 -1 EDGE 1387 1388 2 EDGE 1388 1415 -1 ###Manual### pose_fold_tree = FoldTree(original_pose.total_residue()) pose_fold_tree.new_jump(1, 1388, 1387) original_pose.fold_tree(pose_fold_tree) FOLD_TREE EDGE 1 1387 -1 EDGE 1 1388 1 EDGE 1388 1426 -1

References: https://www.rosettacommons.org/docs/latest/rosetta_basics/structural_concepts/foldtree-overview