1. Outline: The Lymn-Taylor cycle PCA method (theory & applications) Individual involvement coefficient (theory & applications) Summary Future work

2. http://www.sciencemag.org/feature/data/1049155s1.mov

3. The Lymn-Taylor cycle (1)Myosin is bound to actin (2) ATP binds to myosin and then myosin dissociates from actin (3) Hydrolysis of ATP to ADP and Pi leads to a change in conformation for myosin (4) Myosin rebinds to actin and actin is “rowed” past myosin with the release of the hydrolyzed products (ADP and Pi) Geeves & Holmes : Annu. Rev. Biochem. 1999. 68:687–728 Power-Stroke Recovery-Stroke

4. OPEN (3) (2) CLOSED

5. Principal Component Analysis a – number of the first principal components b – the total number of the principal components % - the contribution to the total variance of the data PC1 PC2 we want to simplify the problem by reducing the dimension of the system we want to preserve as much as possible of the original information content

6. MD of S1-Myosin head in OPEN conformation 15 eigenvectors 80%Good projection of data

7. MD of S1-Myosin head in CLOSED conformation ATPADP+Pi Total nr. of eigenvectors = more than 2200 (only Cα atoms)

8. Are we choosing the right eigenvectors?! R P PC1 PC2 PC1 PC2 d1 d2

9. PC1=L 1 PC2=L 2 R P displacement vector I2I2 I1I1 Individual involvement coefficient I k - individual involvement coefficient (X 1 -X 2 ) – displacement vector C k – the cumulative involvement coefficient Li & Cui : Biophysical Journal 2004. 743-763

10. Individual involvement coefficient for different MD trajectories „Important modes“ ????

11. “Important” elements of S1-Myosin head in CLOSED conformation (ATP)

12. “Important” elements: Relay-helix : cyan Switch2-Loop: white Converter Domain: green SH1-Helix : pink Lever Arm : yellow calculate the % from the total variance (PCA) calculate the individual involvement coefficients for some of them visualize the first mode (VMD) Switch2: blue P-Loop: red

13. All “Important” elements

14. „Important“ element: Relay-helix

15. „Important“ element: Converter-domain + lever-arm

16. „Important“ element: Switch2

17. „Important“ element : Switch1

18. „Important“ element : Ploop

19. Summary:  a good projection of the data is obtained with PCA  the mode with the largest contribution  functionally relevant motion  to analyze the conformational change  Individual Involvement Coefficient  the conformational change was decomposed into the motion of some structural elements.