Computer-Aided Drug Design Services |
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p53 - MDM2 oncoprotein drug leads derived from virtual high-throughput screens |
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The Bioinformatics Center provides computational resources and staff expertise in Computer-Aided Drug Design. CADD in used in drug discovery, design, and development research. CADD services are available for CSU researchers and PI's in the Rocky Mountain Regional Center of Excellence in Biodefense. |
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| The benefits of CADD include: | |
| -- Quickly identify novel drug compounds and drug leads | |
| -- Identify new drug analogues | |
| -- Expand existing lead series compounds | |
| -- Complement experimental high-throughput screening efforts | |
| -- Purchase lead compounds directly from fine chemical vendors | |
| CADD screening methods include: | |
| -- Structure-based screens (drug-receptor and protein-ligand docking) | |
| -- Ligand-based screens (pharmacophore and similarity searches) | |
| -- Physicochemical based screens (Lipinski's rules) | |
| -- 3D-shape and 3D-electrostatics based screens | |
| The Center maintains numerous small-molecule compound libraries for CADD screens: | |
| -- Multi-million compound small-molecule libraries; currently 8.5M+ compounds |
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| -- Drug-like, lead-like, and fragment based compounds | |
| -- Natural products and synthetic compounds | |
| -- Diversity-oriented and focused sublibraries | |
| -- Conformers, enantiomers, rotamers, and tautomers for many compounds | |
| CADDSoftware | |
| Currently, the Center utilizes CADD software from OpenEye Scientific Software Inc. OpenEye's software suite is used extensively in academic, government, and commercial drug research. The Center will regularly evaluate other CADD applications, and will consider requests for specific applications from the research community. | |
| CADD Hardware | |
| The Center utilizes its 64-CPU Apple G5 cluster for screening runs, storage of small-molecule compound libraries, bioinformatics analysis, and molecular modeling. | |
| Focused sublibraries for specific disease states and drug targets include: | |
| -- Kinase sublibrary | |
| -- Protease sublibrary | |
| -- GPCR sublibrary | |
| -- Nuclear receptor sublibrary | |
| -- Ion channel sublibrary | |
| -- Adenosine receptor sublibrary | |
| -- FGFR1K sublibrary | |
| -- PDK-1 sublibrary | |
| -- CDK4 sublibrary | |
| -- p38 MAP kinase sublibrary | |
| -- HIV1 protease sublibrary | |
| The screening libraries include the following scaffold compounds: | |
| -- Amidinobarbiturates | |
| -- Imidazolyliminothiazolines | |
| -- Imidazotriazines | |
| -- Isocarbolines | |
| -- Lactams | |
| -- Mesoionic 1,2,3-triazoles | |
| -- Tetrahydroquinolines | |
| -- 1,2,3-thiadiazoles | |
| -- 1,2,3-thiadiazole-5-imines | |
| -- Thiazolines | |
| -- Thiazolylpyrazoles | |
| -- Tryptamines and homotryptamines | |
| The screening libraries include the following building block compounds: | |
| -- Aldehydes | |
| -- Barbiturates | |
| -- Carboxylic acids | |
| -- Primary and cyclic amines | |
| -- Natural compounds and semi-synthetic derivatives | |
| -- Thioamides and mercapto derivatives | |
| The Center includes screening libraries from the following sources: | |
| -- NCI Open Database | |
| -- Harvard Screening Facility -- National Screening Laboratory for the Regional Centers of Excellence in Biodefense and Emerging Infectious Diseases |
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| -- ZINC database | |
| -- InterBioScreen Ltd. | |
| -- LIFE Chemicals | |
| -- Otava Chemicals | |
| -- Asinex | |
| -- Ambinter | |
| -- Albany Molecular Research / Comgenex | |
| Screening services include: | |
| -- Assistance in job preparation, job execution, job management, and job performance analysis on the Apple cluster | |
| -- Molecular modeling of results: high-quality images and videos suitable for publications, grants, and conferences | |
| Molecular Dynamics | |
| Assistance with molecular dynamics simulations is available for modeling time-dependent behavior of macromolecular systems. NAMD and GROMACS are used for MD simulations. Other MD software can be used by request. | |
| For more information contact: | |
| Richard Casey, PhD | |
| Ph: 970-491-8568 | |
| Cell: 970-980-5975 | |
| Email: richard.casey@colostate.edu | |