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Detecting the Native Ligand Orientation by Interfacial Rigidity

Detecting the Native Ligand Orientation by Interfacial Rigidity

"A novel approach to pose selection in protein-ligand docking based on graph theory" presented at the Departmental Retreat at Michigan State University on October 7, 2016

Sebastian Raschka

October 07, 2016
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  1. Biochemistry & Molecular Biology ! Departmental Retreat October 7, 2016;

    Okemos Conference Center ! Sebastian Raschka Leslie A. Kuhn Lab Detecting the Native Ligand Orientation by Interfacial Rigidity
  2. Binding Mode Prediction Crystal structure of the complex between carboxypeptidase

    A and the biproduct analog inhibitor L-benzylsuccinate (PDB code: 1cbx)
  3. Chorismate mutase and prephenate (PDB code: 1com) ProFlex: D. J.

    Jacobs, A. J. Rader, L. A. Kuhn, and M. F. Thorpe (2001) Protein Flexibility Predictions Using Graph Theory. Proteins: 44, 150-165 . near-native binding mode → rigid binding pocket “bad” docking → flexible binding pocket
  4. 2.8 Å RMSD 1.0 Å RMSD Crystal Pose Crystal structure

    of the complex between carboxypeptidase A and the biproduct analog inhibitor L-benzylsuccinate (PDB code: 1cbx)
  5. 3.  New information / signal (cooperativity) 1.  Competitive scoring function

    for binding mode prediction / docking 2.  Robust, no “bad” predictions
  6. http://www.kuhnlab.bmb.msu.edu/software https://psa-lab.github.io/siteinter lock ite nterlock S I R a s

    c h k a , Bemister- Buf fi ng ton , an d Ku hn 2 0 1 6 . P r o t e i n s . D O I : 1 0 . 1 0 0 2 / p r o t . 2 5 1 7 2. (In press.)
  7. PROTEIN STRUCTURE AND ANALYSIS LAB Dr. Leslie Kuhn (Lab. Director)

    Joseph Bemister-Buffington (Undergrad. Researcher) Alex Wolf (Undergrad. Researcher) http://www.kuhnlab.bmb.msu.edu
  8. Chao-Yie Yang R, Wang A, Wang S. A Systematic analysis

    of the effect of small-molecule binding on protein flexibility of the ligand- binding sites. J Med Chem 2005;5648–5650.