1. 2D-classification and 3D-QSAR research of benzimidazole-based respiratory syncytial virus fusion inhibitors Dingjue Ji, Yaojin Sun Department of Bioinformatics and Biostatistics, School of Life Science, Shanghai Jiaotong University 800 Dongchuan RD, Shanghai, China

2. Outline Introduction Methods Results Q&A

3. Introduction “A virus is a small infectious agent that replicates only inside the living cells of other organisms.”

4. Human respiratory syncytial virus Isolated from chimpanzee respiratory health threat to newborn infants and young children. elderly and high-risk adults with underlying chronic pulmonary disease and the severely immunocompromised What is RSV?

5. Impact of RSV 132,000 to 172,000 hospitalizations among children,5 years of age 100,000 to 126,000 hospitalizations among children,1 year of age 1.5 million outpatient visits among children,5 years of age

6. Therapy Palivizumab Medi-534 Ribavirin Cathelicidin More!

7. How we start CoMFA CoMSIA Molecular dynamics simulation Combination!

8. Methods “Chemical biology is a scientific discipline spanning the fields of chemistry, biology, and physics. It involves the application of chemical techniques, tools, and analyses, and often compounds produced through synthetic chemistry, to the study and manipulation of biological systems.”

9. Data sets

10. Molecular Modeling and Alignment 3D structure built by SYBYL modeling program Emphasis on the common structure BMS-433771 examined in vivo benzimidazole, benzimidazolinone, or both

11. Two-dimensional representation

12. Molecular Docking 1G2C Well-defined binding site near Y198 Autodock4.0/Vina package For QSAR model and initial structure of MD

13. CoMFA Models Comparative Molecular Field Analysis Molecules aligned within a lattice which is rife with arranged probe Coulomb potential and Lennard-Jones potential Partial least squares 3:1

14. CoMSIA Models Comparative Molecular Similarity Indices Analysis Five force field Gaussian-type potential

15. Results “Bioinformatics is an interdisciplinary field that develops methods and software tools for understanding biological data.”

16. QSAR models

22. Preprocessing Categorical x [-1,1] with abundance over 80% x Correlation over 80% x Internal coding of perl

23. Classification potent(PEC50>7) and weak(PEC50<7) BP neural network SVM Random Forest Coding of R

24. Preview of BP results pre Potent Weak Potent 147 33 Weak 7 104 pre2 Potent Weak Potent 25 23 Weak 9 22

25. Preview of RF results pre Potent Weak Potent 154 0 Weak 0 137 pre2 Potent Weak Potent 26 15 Weak 8 30

26. Preview of SVM results pre Potent Weak Potent 138 26 Weak 16 111 pre2 Potent Weak Potent 26 16 Weak 8 29

27. Further Works Basic statistics of evaluation Analyze relation between QSAR model and receptor Try to reveal binding mechanism and give advice on modification

28. Q&A “Plato is dear to me, but dearer still is truth.”