Beta Sheet Alignment with Cyclic Coordinate Descent David Arndt - May 18, 2007

Cyclic Coordinate Descent (CCD) CCD algorithm originally used for loop closure Iteratively adjusts torsion angles along a sub- segment of the peptide We use it for:  Closing gaps in a structure  Repairing bad torsion angles for a segment of a peptide, and using CCD to close created gaps  Aligning hydrogen bonds between Beta sheets

Cyclic Coordinate Descent (CCD)

Closing gaps with CCD

Angle repair with CCD

Beta sheet alignment Given list of acceptor and donor residues Align “phatom” O with real O, “phantom” H with real H

Sample hydrogen bonds file Acceptor-Donor pairs. Can include comments. Residue names optional. Can be copied and pasted from VADAR. MET 1 VAL 17 GLN 2 GLU 64 ILE 3 LEU 15 PHE 4 LEU 67 VAL 5 ILE 13 LYS 6 LEU 69 THR 7 GLY 10 # Not called by PyMol for 1xqq_a LYS 11 THR 7 ILE 13 VAL 5 LEU 15 ILE 3 SER 65 PHE 4 LEU 67 LYS 6

Example: ubiquitin (1xqq NMR)

Central strand dislocated

Alignment strategy Find segments of residues with user-specified hydrogen bonds. Gaps of 1 residue allowed. Red = anchor Green = rigid Between = flexible

Repaired structure Too close. PyMol creates covalent bond.

Hydrogens removed

Daggett-like model of PrP Sc (From Mark Berjanskii, Mar 28) DeMarco ML, Daggett V. From conversion to aggregation: protofibril formation of the prion protein. Proc Natl Acad Sci U S A Feb 24;101(8):

Daggett-like model

Beta-sheet misalignment

Minimization with GAFolder Helix

Alignment strategy Red = anchor Green = rigid Between = flexible - First align rigid segment to align hydrogen bonds - Then adjust 2nd flexible region to close gap 1st N-anchor 2nd N-anchor C-anchor 1st flexible region 2nd flexible region

Aligned - but not well ALA 115 tries to align with SER 132, but SER 132 is facing the wrong way

Future directions Use a more refined Daggett-like model from Mark as a starting point Gap closure often fails with short flexible regions  Implement trial-and-error algorithm to try closing a gap with different sets of parameters Omit wrong-facing residues? Something more sophisticated?

Thanks Dr. Wishart Raj Maiti Mark Berjanskii Cam Macdonell Marie-Aude Coutouly Dr. David Case