Howard University: Center for Computational Biology and Bioinformatics
- 1. Howard University: Center for Computational Biology & Bioinformatics
- 2. Biochemistry & Molecular Chemistry NHGC Sys & Comp Biology Science
- 3. H st or i cal D i evel opment of t he CB… CB 1989 Faculty Research Laboratory MD/MM 1995 Faculty Research Laboratory MD/MM, QSAR 1997 Laboratory of Molecular Computations (LMC) MD/MM, QSAR 2003 Laboratory of Molecular Computations & Bioinformatics (LMCB) MD/MM, QSAR, Comp. Chemistry, Statistical Genetics & Bioinformatics 2006 Center for Computational Biology & Bioinformatics (CCBB) MD/MM, QSAR, Comp. Chemistry, Statistical Genetics & Bioinformatics, other
- 4. R i onal e and N at eed f or t he C B CB The Howard University Strategic Framework for Action II (SFAII) • Encourage the interaction among mathematicians, scientists (biomedical, chemists, biologists, physicists, engineers), and computer-based scientists in the resolution of complex disease processes. • Encourage multi-disciplinary approaches to research.
- 5. CCBB Re s i d e nt Pe r s o nne l … 2003- 2008 Dr. William M. Southerland Dr. Zengjian Hu Professor & Director Res. Assistant Professor Molecular modeling Molecular modeling molecular dynamics molecular dynamics virtual database development virtual ligand screening Dr. Yayin Fang Mr. Guy Lingani Res. Assistant Professor Lab/IT Manager Molecular dynamics System/network administrator ab initio calculations. Laboratory Manager Mr. Joseph Gill Dr. Qingqi Yue Research Assistant Research Associate Computer science, Analysis of genetic data and hardware cluster computer programming for development genetics data analysis.
- 7. CCBB Compute Resources Year # of Installe Resource Type Processors Nodes # of CPU's d Gflops SGI Origin 200 Rack Mounted 180 MHz 3 6 2000 2.16 SGI Indigo2 (joy2) 75 MHz 1 1 2002 0.15 SGI Indigo (joy) 75 MHz 1 1 2002 0.15 SGI Octane2 (joy4) 195 MHz 2 2 2002 0.78 SGI Octane2 (joy5) 250 MHz 2 3 2002 1 SGI Tezro dual cpu's 800 MHz 3 6 2004 9.6 SGI Fuel 800 MHz 1 1 2004 1.6 Linux Cluster dual cpu's (biocluster) 3.20 GHz 7 14 2004 89.6 Linux Cluster (Bio2001 & Bio2003) 3.20 GHz 2 4 2004 25.6 Linux Quad Cluster Dual CPU’s (bee) 3.20 GHz 7 56 2006 291.2 Linux cluster (elephant) 3.20 GHz 1 4 2007 25.6 447.44 30 Total Nodes 98 CPU 's Gflops
- 8. C B -H N C B U et Cont ext …
- 11. Cent er f or C put at i onal om B ol ogy & B oi nf or m i cs… i i at (C B ) CB Protein targeted drug design QSAR structure design Genome based drug design New biomaterial design Statistical genetics Classification of protein folds Prediction of domain boundaries in proteins Development of inter-residues contacts database Prediction of protein inter-residue contact clusters maps Virtual high throughput ligand screening @Howard University, Medicinal Indiana University-Purdue Chemistry, Pharmacology, Dentistry, University Indianapolis, Texas Cancer Center, Systems & Computer A&M University-Corpus Sciences Christi
- 12. Resour ce Shar i ng… Center for Statistical National Human Computational Genome Center Biology & Genetics & Bioinformatics Bioinformatics Personnel Software Hardware
- 13. Resour ce Shar i ng… Cont ’d Computational Proteomics Center for Department of Computational Systems & Biology & Computer Bioinformatics Sciences Personnel Hardware Software
- 14. I nt er act i on W t h O her H i t U Faci l i t i es… Howard University Imaging Facility National Human Genome Center (NHGC) General Clinical Research Center (GCRC)
- 15. I m ng I nf or m i cs Suppor t agi at Act i vi t i es… Molecular design for targeted nanoparticles Computational support for image resolution and refinement
- 16. CCBB GCRC NHGC IT Support for CCBB, GCRC, and NHGC
- 17. Exam e of R pl esear ch pr oj ect Salvianolic acid B as a targeting agent for development of a Cox-2 targeted therapy for drug resistant head and neck cancer Barnase thermal titration Via MD simulation – detection of early denaturation sites 3D-QSAR study of novel anticonvulsant enaminones Small Molecule DNA Recognition
- 18. Molecular Dynamics Simulation of Netropsin Binding to DNA: Genome-Base Drug Design
- 19. Netropsin + DNA 5’-CGCGAATTCGCG-3’ ******** 3’-GCGCTTAAGCGC-5’
- 20. 5’-CTTAATTCGAATTAAG-3’ 3’-GAATTAAGCTTAATTC-5’ N-terminal fragment of Moloney murine leukemia virus (NMLV) Reverse Transcriptase (RT) Netropsin
- 21. Systems calculated 16 base pairs of d(CTTAATTCGAATTAAG)2 Free DNA Free Netrospin Netropsin molecule only Two netropsin molecules bound in the minor groove DNA Netrospin complex of DNA d(CTTAATTCGAATTAAG)2
- 22. 74.68×70.86×48.997 (Angstroms3) 6109 waters
- 23. Binding Orientation 5’-CTTAATTCGAATTAAG-3’ A G G A 3’-GAATTAAGCTTAATTC-5’ Amidinium Guanidiniu m
- 24. Comparison of RMS deviation of free DNA and DNA in Complex
- 25. D i ni t i on of t he w dt h ef i of D A m nor gr oove N i Dis1 Dis2 Dis3 Dis4 Dis5 Dis6 Dis7 Dis8 Closest distance between two phosphates Dis9 on different strands of DNA cross the minor groove. Dis10 Dis1 1 Dis12
- 27. Width of the minor groove of DNA in complex with Netropsin NT1 Dis 2 Dis 5 Dis 7 NT2 Dis 11
- 28. BI: 120 ≤ ε ≤ 210 and 235 ≤ ζ ≤ 295 BII: 210 ≤ ε ≤ 300 and 150 ≤ ζ ≤ 210
- 29. DNA in Complex Free DNA
- 30. H-bond NT1 NT2
- 31. Binding Energy EComplex EDNA-Free ENetropsin-Free ∆E 1690.17 4533.28 -10.964 -2821.18 ∆ E = EComplex – EDNA-Free – 2*ENetropsin-Free EComplex EDNA-In-Complex ELigand-In-Complex ∆E 1690.17 4516.13 38.97 -2864.93 ∆ E = EComplex – EDNA-In-Complex –E(NT1+NT2)-In-Complex
- 32. Summary 1. Molecular dynamic simulation show that the properties of the ligand and DNA contribute to the DNA-ligand binding. 3. The study can be used to design and develop new anti-tumor agent that will be able to selectively bound to the specific A/T or, in the future, G/C rich regions of DNA.
- 33. Acknow edgem s… l ent This work is supported by 2 G12 RR003048 from the RCMI Program, Division of Research Infrastructure, National Center for Research Resources, NIH Dr. William M Southerland Dr. Legand Burge Dr. Vernon R. Morris Dr. Chunmei Liu Dr. Zengjian Hu Dr. Eugene Billiot Mr. Guy Lingani Dr. Qingqi Yue Dr. George Bonney Dr. Angela Jackson Dr. Eric C. Long Dr. Kenneth R. Scott Dr. Xinbin Gu Dr. Patrice Jackson Dr. Tadasha Culbreath Mr. Donnell Scott
- 34. Thank you from….CCBB Howard University