The ins and outs of docking in drug design.pptx

Reviewing docking studies, accuracy issues, and considerations for reliable drug design.

1. The ins and outs of docking in drug design Reviewing docking studies, accuracy issues, and considerations for reliable drug design.

2. Docking Considerations Virtual Screening Docking in virtual screening and lead optimization. Key Issues Issues to consider when undertaking a docking study. Accuracy Range Accuracy can change from 0% to 92.66%. Final Warning Beware of docking! Proceed with caution.

3. Structure-Based Drug Design Docking Power Powerful tool in drug screening processes. CADD Essential Structure-based drug design is essential. Ligand Orientation Predicts ligand orientation bound to protein. Paper Increase Rapid increase in docking-related papers.

4. Docking Algorithms Ligand Fitting Algorithms fit ligand into receptor protein. Speed vs Accuracy Balance between speed and accuracy needed. Scoring Functions Algorithms vary by scoring functions used. Binding Priority Binding affinity is a virtual screening priority.

5. Docking Software AutoDock Widely used docking software. GOLD Genetic algorithm docking program. Glide Exhaustive search-based docking program. Rosetta Predict protein structure for docking.

6. Docking Software Stats 30 Programs Number of docking programs listed. 20 Webservers Number of docking webservers listed. 10 Screening Number of screening software listed.

7. Pre-Docking Steps Protein Availability Is the protein structure available and reliable? Sequence Needed Protein sequence must be available. Structure Needed Protein structure must be available. Preparation Protein and ligand prepared well for docking.

8. Docking Methods Water Varying presence/absence of water. PH Levels Varying pH levels in the process. Conformation Flexible docking allows shifts. Rigid Docking Protein and ligand are fixed.

9. Scoring Function Gibbs Energy Lower energy indicates stable complex. Algorithm Variety Different algorithms for different needs. Regression Based Weighted-scoring based on regression coefficients. Scoring Functions Many scoring functions are available.

10. Docking Accuracy Target Protein Best program for target protein needed. Regression Regression of bioactivity versus scoring function. iSMART Tool Website integrates TCM and iSMART tool. Accuracy Rate Accuracy higher than 70%.

11. Agonist or Inhibitor Dock Score Dock score indicates good inhibitor/agonist? Binding Affinity Docking program provides binding affinity. Overinterpretation Not advisable to overinterpret docking results. Bioassays Further validation of bioassays needed.

12. Ligand-Based Studies R Square Good R square in ligand-based model. 100 Percent Structure-based results inconsistent. 1 Database Virtual screening is database-dependent.

13. MD Simulation MD Validation Lack of further validation of MD simulation. Binding Affinity Docking calculates the binding affinity only. Complex Shape MD emphasizes complex shape changes. Essential Validation MD simulation is an essential validation.

14. Concluding Remarks Validation Validation of MD studies is important. Inaccurate Picture Docking alone creates inaccurate picture. Draw Conclusions Draw conclusions carefully with docking. Important Issue Questionable docking results are important.