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
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2D-classification and 3D-QSAR research of benzimidazole-based respiratory syncytial virus fusion inhibitors Dingjue Ji, Yaojin Sun Department of Bioinformatics.
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2D-classification and 3D-QSAR research of benzimidazole-based respiratory syncytial
virus fusion inhibitorsDingjue Ji, Yaojin Sun
Department of Bioinformatics and Biostatistics, School of Life Science, Shanghai Jiaotong University
800 Dongchuan RD, Shanghai, China
Outline
•Introduction
•Methods
•Results
•Q&A
Introduction“A virus is a small infectious agent that replicates only inside the living cells of other organisms.”
•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?
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
Therapy
•Palivizumab
•Medi-534
•Ribavirin
•CathelicidinMore!
How we start
•CoMFA
•CoMSIA
•Molecular dynamics simulationCombination!
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.”
Data sets
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
Two-dimensional representation
Molecular Docking
•1G2C
•Well-defined binding site near Y198
•Autodock4.0/Vina package
•For QSAR model and initial structure of MD
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
CoMSIA Models
•Comparative Molecular Similarity Indices Analysis
•Five force field
•Gaussian-type potential
Results“Bioinformatics is an interdisciplinary field that develops methods and software tools for understanding biological data.”
QSAR models
QSAR models
QSAR models
QSAR models
QSAR models
QSAR models
Preprocessing
Categorical x
[-1,1] with abundance over 80% x
Correlation over 80% x
Internal coding of perl
Classification
potent(PEC50>7) and weak(PEC50<7)BP neural network