- Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy
Richard A Friesner
Department of Chemistry, Columbia University, New York, New York 10036, USA
J Med Chem 47:1739-49. 2004
..Glide is also found to be more accurate than the recently described Surflex method...
- A novel integrated framework and improved methodology of computer-aided drug design
Calvin Yu chian Chen
College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China
Curr Top Med Chem 13:965-88. 2013
Computer-aided drug design (CADD) is a critical initiating step of drug development, but a single model capable of covering all designing aspects remains to be elucidated...
- Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening
Thomas A Halgren
Schrodinger, L L C, 120 W 45th Street, New York, New York 10036, USA
J Med Chem 47:1750-9. 2004
..Comparisons to results for the thymidine kinase and estrogen receptors published by Rognan and co-workers (J. Med. Chem. 2000, 43, 4759-4767) show that Glide 2.5 performs better than GOLD 1.1, FlexX 1.8, or DOCK 4.01...
- Network pharmacology: the next paradigm in drug discovery
Andrew L Hopkins
Division of Biological Chemistry and Drug Discovery, College of Life Science, University of Dundee, Dundee, UK
Nat Chem Biol 4:682-90. 2008
..Advances in these areas are creating the foundation of the next paradigm in drug discovery: network pharmacology...
- Targeting cancer with small molecule kinase inhibitors
Dana Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Nat Rev Cancer 9:28-39. 2009
..This Review provides a broad overview of some of the approaches currently used to discover and characterize new kinase inhibitors...
- Natural products in drug discovery
Alan L Harvey
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK
Drug Discov Today 13:894-901. 2008
..It is hoped that the more efficient and effective application of natural products will improve the drug discovery process...
- Drug repositioning: identifying and developing new uses for existing drugs
Ted T Ashburn
Dynogen Pharmaceuticals, Inc, 31 St James Avenue, Suite 905, Boston, Massachusetts 02116, USA
Nat Rev Drug Discov 3:673-83. 2004
- Improved protein-ligand docking using GOLD
Marcel L Verdonk
Astex Technology, Ltd, Cambridge, United Kingdom
Proteins 52:609-23. 2003
..Even at docking speeds of around 1-2 min/compound, the Goldscore function predicts binding energies with a standard deviation of approximately 10.5 kJ/mol...
- Can the pharmaceutical industry reduce attrition rates?
Basic Research at Merck Research Labs, 126 East Lincoln Avenue, Rahway, New Jersey 07075, USA
Nat Rev Drug Discov 3:711-5. 2004
- DrugBank: a knowledgebase for drugs, drug actions and drug targets
David S Wishart
Department of Computing Science, University of Alberta, Edmonton, AB, Canada T6G 2E8
Nucleic Acids Res 36:D901-6. 2008
..Since its first release in 2006, DrugBank has been widely used to facilitate in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical ..
- Extended-connectivity fingerprints
J Chem Inf Model 50:742-54. 2010
..While the use of ECFPs has been widely adopted and validated, a description of their implementation has not previously been presented in the literature...
- Ligand efficiency: a useful metric for lead selection
Andrew L Hopkins
Drug Discov Today 9:430-1. 2004
- Drugs for bad bugs: confronting the challenges of antibacterial discovery
David J Payne
Infectious Diseases Centre of Excellence for Drug Discovery, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA
Nat Rev Drug Discov 6:29-40. 2007
- Relating protein pharmacology by ligand chemistry
Michael J Keiser
Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th St, San Francisco California 94143 2550, USA
Nat Biotechnol 25:197-206. 2007
..These predictions were subsequently confirmed experimentally. Relating receptors by ligand chemistry organizes biology to reveal unexpected relationships that may be assayed using the ligands themselves...
- iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan
Tsung Ying Tsai
Laboratory of Computational and Systems Biology, School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan
J Comput Aided Mol Des 25:525-31. 2011
..iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file ..
- LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters
Inte Ligand GmbH, Mariahilferstrasse 74B 11, A 1070 Vienna, Austria
J Chem Inf Model 45:160-9. 2005
..The algorithms for ligand extraction and interpretation as well as the pharmacophore creation technique from the automatically interpreted data are presented and applied to a rhinovirus capsid complex as application example...
- Benchmarking sets for molecular docking
Department of Pharmaceutical Chemistry, University of California San Francisco, QB3 Building, 1700 4th Street, Box 2550, San Francisco, California 94143 2550, USA
J Med Chem 49:6789-801. 2006
..DUD is freely available online as a benchmarking set for docking at http://blaster.docking.org/dud/...
- APD2: the updated antimicrobial peptide database and its application in peptide design
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
Nucleic Acids Res 37:D933-7. 2009
..Using frequently occurring residues, we demonstrate database-aided peptide design in different ways. Among the three peptides designed, GLK-19 showed a higher activity against Escherichia coli than human LL-37...
- ZINC--a free database of commercially available compounds for virtual screening
John J Irwin
Department of Pharmaceutical Chemistry, University of California San Francisco, Genentech Hall, 600 16th Street, San Francisco, California 94143, USA
J Chem Inf Model 45:177-82. 2005
..Users can process their own molecules by uploading them to a server. Our hope is that this database will bring virtual screening libraries to a wide community of structural biologists and medicinal chemists...
- The efficiency of multi-target drugs: the network approach might help drug design
Department of Medical Chemistry, Semmelweis University, PO Box 260, H 1444 Budapest 8, Hungary
Trends Pharmacol Sci 26:178-82. 2005
Despite considerable progress in genome- and proteome-based high-throughput screening methods and rational drug design, the number of successful single-target drugs did not increase appreciably during the past decade...
- The evolving role of natural products in drug discovery
Frank E Koehn
Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA
Nat Rev Drug Discov 4:206-20. 2005
- Potential mechanisms of atypical antipsychotic-induced metabolic derangement: clues for understanding obesity and novel drug design
Institute of Neuroscience, National Research Council C N R, Via del Fosso di Fiorano, 64 00143 Roma, Italy
Pharmacol Ther 127:210-51. 2010
..For this reason, recently identified obesogenic and diabetogenic mechanisms are the background on which the present work is built and some novel forthcoming lines of investigation suggested...
- A 'rule of three' for fragment-based lead discovery?
Astex Technology Ltd, 436 Cambridge Science Park, Milton Road, CB4 0QA, Cambridge, UK
Drug Discov Today 8:876-7. 2003
- A critical assessment of docking programs and scoring functions
Gregory L Warren
GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA
J Med Chem 49:5912-31. 2006
..For prediction of compound affinity, none of the docking programs or scoring functions made a useful prediction of ligand binding affinity...
- SuperTarget and Matador: resources for exploring drug-target relationships
Structural Bioinformatics Group, Institute of Molecular Biology and Bioinformatics, Charite University Medicine Berlin, Arnimallee 22, 14195 Berlin, Germany
Nucleic Acids Res 36:D919-22. 2008
..SuperTarget and Matador are available at http://insilico.charite.de/supertarget and http://matador.embl.de...
- Docking and scoring in virtual screening for drug discovery: methods and applications
Douglas B Kitchen
Department of Computer Aided Drug Discovery, Albany Molecular Research, Inc, 21 Corporate Circle, Albany, New York 12212 5098, USA
Nat Rev Drug Discov 3:935-49. 2004
..Here, we review key concepts and specific features of small-molecule-protein docking methods, highlight selected applications and discuss recent advances that aim to address the acknowledged limitations of established approaches...
- Soft drug design: general principles and recent applications
Center for Drug Discovery, University of Florida, Health Science Center, P O Box 100497, Gainesville, Florida 32610 0497, USA
Med Res Rev 20:58-101. 2000
Soft drug design represents a new approach aimed to design safer drugs with an increased therapeutic index by integrating metabolism considerations into the drug design process...
- Integrated Modeling Program, Applied Chemical Theory (IMPACT)
Jay L Banks
Schrodinger, Inc, New York, NY 10036, USA
J Comput Chem 26:1752-80. 2005
- Natural products as leads to potential drugs: an old process or the new hope for drug discovery?
David J Newman
Natural Products Branch, Developmental Therapeutics Program, DCTD, National Cancer Institute Frederick, P O Box B, Frederick, Maryland 21702, USA
J Med Chem 51:2589-99. 2008
- Novel inhibitor design for hemagglutinin against H1N1 influenza virus by core hopping method
Xiao Bo Li
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics Theranostics, School of Pharmacy, Tianjin Medical University, Tianjin, China
PLoS ONE 6:e28111. 2011
..to subsequently penetrate into the infected cell, hemagglutinin (HA) has become one of the main targets for drug design against influenza virus...
- Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by high-throughput screening
Department of Medicine, UCSF, San Francisco, California 94143 0521, USA
J Clin Invest 115:2564-71. 2005
..Small-molecule correctors may be useful in the treatment of CF caused by the DeltaF508 mutation...
- Evolutionary and immunological implications of contemporary HIV-1 variation
Division of Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico 98545, USA
Br Med Bull 58:19-42. 2001
..The impact of HIV-1 variation on host immune response is reviewed in this context...
- The properties of known drugs. 1. Molecular frameworks
G W Bemis
Vertex Pharmaceuticals, Cambridge, Massachusetts 02139 4242, USA
J Med Chem 39:2887-93. 1996
..We discuss the possible interpretations of these findings and the way they may be used to guide future drug discovery research...
- Pharmacogenomics: translating functional genomics into rational therapeutics
W E Evans
Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Science 286:487-91. 1999
- Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK)
J Jean Cui
La Jolla Laboratories, Pfizer Worldwide Research and Development, San Diego, California 92121, USA
J Med Chem 54:6342-63. 2011
..domain, revealed a novel ATP site environment, which served as the target to guide parallel, multiattribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions ..
- The cystine knot motif in toxins and implications for drug design
D J Craik
Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia
Toxicon 39:43-60. 2001
..and their unique structural scaffold can be harnessed for molecular engineering applications and in drug design. Applications of cystine knot molecules for the treatment of pain, and their potential use in antiviral and ..
- Structure and functionality in flavivirus NS-proteins: perspectives for drug design
Department of Biomolecular Sciences and Biotechnology, University of Milano, Via Celoria 26, 20133 Milano, Italy
Antiviral Res 87:125-48. 2010
..Nevertheless, up to few years ago flaviviruses were considered low interest candidates for drug design. At the start of the European Union VIZIER Project, in 2004, just two crystal structures of protein domains ..
- Lessons learnt from assembling screening libraries for drug discovery for neglected diseases
University of Dundee, College of Life Sciences, James Black Centre, Dow Street, Dundee DD1 5EH, UK
ChemMedChem 3:435-44. 2008
..The implications of this study for compound selection, especially in an academic environment with limited resources, are considered...
- The resurgence of covalent drugs
Avila Therapeutics, 100 Beaver Street, Waltham, Massachusetts 02453, USA
Nat Rev Drug Discov 10:307-17. 2011
- High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv
Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
Tuberculosis (Edinb) 89:334-53. 2009
..taacf.org), a large, medicinally relevant chemical library was screened against M. tuberculosis strain H37Rv. The screening methods and a medicinal chemistry analysis of the results are reported herein...
- Ligand-based dual target drug design for H1N1: swine flu--a preliminary first study
Chien yu Chen
Laboratory of Pharmacoinformatics and Nanotechnology Department of Biological Science and Technology, China Medical University Taichung, 40402, Taiwan
J Biomol Struct Dyn 27:171-8. 2009
..Nevertheless, the present study is clear, consistent and could give a rational explanation for the binding mode of the best selected ligand...
- Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders
P Jeffrey Conn
Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, 1215 Light Hall, Nashville, Tennessee 37232, USA
Nat Rev Drug Discov 8:41-54. 2009
..These compounds provide high selectivity, novel modes of efficacy and may lead to novel therapeutic agents for the treatment of multiple psychiatric and neurological human disorders...
- Metabonomics: a platform for studying drug toxicity and gene function
Jeremy K Nicholson
Biological Chemistry Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, South Kensington, London SW7 2AZ, UK
Nat Rev Drug Discov 1:153-61. 2002
..Metabonomics is a systems approach for studying in vivo metabolic profiles, which promises to provide information on drug toxicity, disease processes and gene function at several stages in the discovery-and-development process...
- Antibiotics for emerging pathogens
Michael A Fischbach
Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA
Science 325:1089-93. 2009
- Comparative assessment of scoring functions on a diverse test set
State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, P R China
J Chem Inf Model 49:1079-93. 2009
Scoring functions are widely applied to the evaluation of protein-ligand binding in structure-based drug design. We have conducted a comparative assessment of 16 popular scoring functions implemented in main-stream commercial software or ..
- Further development and validation of empirical scoring functions for structure-based binding affinity prediction
Medical Chemistry and Comprehensive Cancer Center, University of Michigan, Ann Arbor 48109 0934, USA
J Comput Aided Mol Des 16:11-26. 2002
..Our results show that this consensus scoring function improves the docking accuracy considerably when compared to the conventional force field computation used for molecular docking...
- Transient pockets on protein surfaces involved in protein-protein interaction
Center for Bioinformatics, Building C7 1, P O Box 151150, D 66041 Saarbruecken, Germany
J Med Chem 50:3457-64. 2007
- Therapeutic potential of venom peptides
Richard J Lewis
Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia
Nat Rev Drug Discov 2:790-802. 2003
..Here we survey the pharmacology of venom peptides and assess their therapeutic prospects...
- Escape from flatland: increasing saturation as an approach to improving clinical success
Wyeth Research, Chemical Sciences, Cambridge, Massachusetts 02140, USA
J Med Chem 52:6752-6. 2009
..In an attempt to explain these observations, we further demonstrate that saturation correlates with solubility, an experimental physical property important to success in the drug discovery setting...
- Subcellular targeting strategies for drug design and delivery
Systems and Cell Biology of Neurodegeneration, Division of Psychiatry Research, University of Zurich, Zurich, Switzerland
Nat Rev Drug Discov 9:29-42. 2010
Many drug targets are localized to particular subcellular compartments, yet current drug design strategies are focused on bioavailability and tissue targeting and rarely address drug delivery to specific intracellular compartments...
- Calculation of protein-ligand binding affinities
Michael K Gilson
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA
Annu Rev Biophys Biomol Struct 36:21-42. 2007
..Ultimately, major improvements in modeling accuracy will likely require advances on multiple fronts, as well as continued validation against experiment...
- DrugBank: a comprehensive resource for in silico drug discovery and exploration
David S Wishart
Department of Computing Science, University of Alberta, Edmonton, AB, Canada T6G 2E8
Nucleic Acids Res 34:D668-72. 2006
..Potential applications of DrugBank include in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical ..
- Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus
John J Dwyer
Trimeris Inc, 3500 Paramount Parkway, Morrisville, NC 27560, USA
Proc Natl Acad Sci U S A 104:12772-7. 2007
..The potent antiviral activity against resistant viruses, the difficulty in generating resistant virus, and the extended half-life in vivo make this class of fusion inhibitor peptide attractive for further development...
- Structural biology of insulin and IGF1 receptors: implications for drug design
Pierre De Meyts
Receptor Biology Laboratory, Hagedorn Research Institute, Niels Steensens Vej 6, DK 2820 Gentofte, Denmark
Nat Rev Drug Discov 1:769-83. 2002
- Intramolecular hydrogen bonding in medicinal chemistry
Discovery Chemistry, F Hoffmann La Roche AG, CH 4070 Basel, Switzerland
J Med Chem 53:2601-11. 2010
..A number of general guidelines for medicinal chemists emerge from this study...
- An introduction to QT interval prolongation and non-clinical approaches to assessing and reducing risk
Chris E Pollard
Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, Cheshire, UK
Br J Pharmacol 159:12-21. 2010
..The non-clinical data are essential to inform decisions about compound progression and to optimize the design of clinical QT studies...
- Similarity-based virtual screening using 2D fingerprints
Krebs Institute for Biomolecular Research and Department of Information Studies, University of Sheffield, 211 Portobello, Sheffield S1 4DP, UK
Drug Discov Today 11:1046-53. 2006
..We demonstrate the effectiveness of this approach to screening, and also describe an approximate form of group fusion, turbo similarity searching, that can be used when just a single reference structure is available...
- HIV vaccine design and the neutralizing antibody problem
Dennis R Burton
Departments of Immunology and Molecular Biology, Scripps Research Institute, La Jolla, California, USA
Nat Immunol 5:233-6. 2004
- Structural biology in fragment-based drug design
Christopher W Murray
Astex Therapeutics Ltd, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom
Curr Opin Struct Biol 20:497-507. 2010
..We focus on antimicrobial research where fragment-based drug discovery allows control of the physical properties of the emerging lead molecule...
- ADMET in silico modelling: towards prediction paradise?
Han van de Waterbeemd
Pfizer Global Research and Development, PDM, Sandwich, Kent CT13 9NJ, UK
Nat Rev Drug Discov 2:192-204. 2003
..Here, we describe how in silico approaches will further increase our ability to predict and model the most relevant pharmacokinetic, metabolic and toxicity endpoints, thereby accelerating the drug discovery process...
- The many roles of computation in drug discovery
William L Jorgensen
Department of Chemistry, Yale University, New Haven, CT 06520 8107, USA
Science 303:1813-8. 2004
..Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for determining protein-ligand binding...
- Multi-target therapeutics: when the whole is greater than the sum of the parts
Grant R Zimmermann
CombinatoRx Inc, 245 First Street, Cambridge, MA 02142, USA
Drug Discov Today 12:34-42. 2007
- Novel computational approaches to polypharmacology as a means to define responses to individual drugs
Department of Computer Science, Hunter College, The City University of New York, New York, New York 10065, USA
Annu Rev Pharmacol Toxicol 52:361-79. 2012
..Although such is a future objective, we review recent progress and challenges in computational techniques that enable the prediction and analysis of in vitro and in vivo drug-response phenotypes...
- A semiempirical free energy force field with charge-based desolvation
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92102, USA
J Comput Chem 28:1145-52. 2007
..The force field shows improvement in redocking simulations over the previous AutoDock3 force field...
- Structure of protein interaction networks and their implications on drug design
Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
PLoS Comput Biol 5:e1000550. 2009
..Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects...
- Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design
Paul G Wyatt
Astex Therapeutics Ltd, 436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, United Kingdom
J Med Chem 51:4986-99. 2008
..Optimisation of cellular activity and characterization of pharmacokinetic properties led to the identification of 33 (AT7519), which is currently being evaluated in clinical trials for the treatment of human cancers...
- Structural basis for understanding oncogenic p53 mutations and designing rescue drugs
Andreas C Joerger
Cambridge University Chemical Laboratory and Cambridge Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom
Proc Natl Acad Sci U S A 103:15056-61. 2006
..g., temperature sensitivity). Some mutants have the potential of being rescued by a generic stabilizing drug. In addition, a mutation-induced crevice is a potential target site for a mutant-selective stabilizing drug...
- The state of the art in anti-malarial drug discovery and development
Jeremy N Burrows
Medicines for Malaria Venture, ICC, Geneva, Switzerland
Curr Top Med Chem 11:1226-54. 2011
..This review summarises the antimalarials developed and registered thus far, as well as describing some of the new small molecule therapy approaches being developed as a contribution towards the malaria eradication agenda...
- Atomic interactions and profile of small molecules disrupting protein-protein interfaces: the TIMBAL database
Alicia P Higueruelo
Department of Biochemistry, University of Cambridge, UK
Chem Biol Drug Des 74:457-67. 2009
..The database provides a resource that will allow further insights into the types of molecules favoured by protein interfaces and provide a background to continuing work in this area. Access at http://www-cryst.bioc.cam.ac.uk/timbal...
- Surflex-Dock 2.1: robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search
Ajay N Jain
Department of Biopharmaceutical Sciences, UCSF Cancer Research Institute, University of California San Francisco, Box 0128, San Francisco, CA 94143 0128, USA
J Comput Aided Mol Des 21:281-306. 2007
- Combining docking and molecular dynamic simulations in drug design
Computational Proteomics Group, John Curtin School of Medical Research, The Australian National University, Canberra ACT 0200, Australia
Med Res Rev 26:531-68. 2006
..Despite a shaky early history, computer-aided drug design techniques can now be effective in reducing costs and speeding up drug discovery...
- From in silico target prediction to multi-target drug design: current databases, methods and applications
Unilever Centre for Molecular Sciences Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom
J Proteomics 74:2554-74. 2011
..Finally, we will conclude with the prospective application of databases to not only predict, retrospectively, the protein targets of a small molecule, but also how to design ligands with desired polypharmacology in a prospective manner...
- Amphipathic alpha helical antimicrobial peptides
Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, Italy
Eur J Biochem 268:5589-600. 2001
..The simple guidelines obtained in this study allowed the design of highly active shortened AMPs and may be generally useful in the development of this type of peptides as anti-infective agents...
- Enterovirus 71 and coxsackievirus A16 3C proteases: binding to rupintrivir and their substrates and anti-hand, foot, and mouth disease virus drug design
Chinese Academy of Sciences, Beijing 100101, China
J Virol 85:10319-31. 2011
..In conclusion, the detailed characterization of both proteases in this study could direct us to a proposal for rational design of EV71/CVA16 3C inhibitors...
- G-quadruplexes: targets in anticancer drug design
Tian Miao Ou
School of Pharmaceutical Science, Sun Yat Sen University, Guangzhou 510080, People s Republic of China
ChemMedChem 3:690-713. 2008
..As drug design targets, the topology and structural characteristics of quadruplexes, their possible biological roles, and the ..
- Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria
Richard T Eastman
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, Hammer Health Sciences Center, Room 1502, 701 West 168th Street, New York 10032, New York, USA
Nat Rev Microbiol 7:864-74. 2009
..This Review article discusses our current knowledge about the mode of action of ACTs, their pharmacological properties and the proposed mechanisms of drug resistance...
- Improved therapeutic targeting of the androgen receptor: rational drug design improves survival in castration-resistant prostate cancer
Ai Chiin Lim
Section of Medicine, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, United Kingdom
Curr Drug Targets 14:408-19. 2013
..Rationally-designed approaches combining different strategies for targeting the AR or associated pathways also warrant clinical evaluation...
- Structure-based and ligand-based drug design for HER 2 receptor
Hung jin Huang
Laboratory of Computational and Systems Biology, School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan, ROC
J Biomol Struct Dyn 28:23-37. 2010
..In this study, both structure-based and ligand-based drug design were employed to design novel HER2 inhibitors from traditional Chinese medicine (TCM)...
- Recent developments in fragment-based drug discovery
Astex Therapeutics Ltd, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK
J Med Chem 51:3661-80. 2008
- 970 million druglike small molecules for virtual screening in the chemical universe database GDB-13
Lorenz C Blum
Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3, CH 3012 Berne, Switzerland
J Am Chem Soc 131:8732-3. 2009
..With 977,468,314 structures, GDB-13 is the largest publicly available small organic molecule database to date...
- Binding properties of human telomeric quadruplex multimers: a new route for drug design
Department of Chemistry P Corradini, University of Naples Federico II, Via Cintia, 4, I 80126 Napoli, Italy
Biochimie 93:1392-400. 2011
..The existence of quadruplex-quadruplex interfaces in the full length telomeric overhang may provide an advantageous factor in drug design to enhance both affinity and selectivity for DNA telomeric quadruplexes.
- Scoring functions and their evaluation methods for protein-ligand docking: recent advances and future directions
Sheng You Huang
Department of Physics and Astronomy, Department of Biochemistry, Dalton Cardiovascular Research Center, and Informatics Institute, University of Missouri, Columbia, MO 65211, USA
Phys Chem Chem Phys 12:12899-908. 2010
The scoring function is one of the most important components in structure-based drug design. Despite considerable success, accurate and rapid prediction of protein-ligand interactions is still a challenge in molecular docking...
- MIND-BEST: Web server for drugs and target discovery; design, synthesis, and assay of MAO-B inhibitors and theoretical-experimental study of G3PDH protein from Trichomonas gallinae
Department of Microbiology and Parasitology, University of Santiago de Compostela, Spain
J Proteome Res 10:1698-718. 2011
..and MAO-A and MAO-B pharmacological assay of eight rasagiline derivatives, promising for anti-Parkinson drug design. In experiment 2, we report sampling, parasite culture, sample preparation, 2-DE, MALDI-TOF and -TOF/TOF MS, ..
- Recent progress in fragment-based lead discovery
Michèle N Schulz
YSBL, University of York, York YO10 5YW, United Kingdom
Curr Opin Pharmacol 9:615-21. 2009
..Here, we provide a brief summary of the key elements of fragment-based lead discovery (FBLD), review recent progress and provide a perspective on the challenges that remain for the field...
- Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design
Joseph D Bauman
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA
Nucleic Acids Res 36:5083-92. 2008
..The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs...
- Computer-aided drug-discovery techniques that account for receptor flexibility
Jacob D Durrant
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA
Curr Opin Pharmacol 10:770-4. 2010
- Casein Kinase II: an attractive target for anti-cancer drug design
Ismail Muhamad Hanif
Experimental Therapeutics Centre, Agency for Science, Technology and Research A STAR, Singapore
Int J Biochem Cell Biol 42:1602-5. 2010
..Here we provide a succinct account of the biology of CK2, its cellular substrates, its pro-survival and pro-proliferation activity, and highlight evidence for its involvement in human cancer...
- Customizing scoring functions for docking
Tuan A Pham
University of California, San Francisco, Box 0128, San Francisco, CA 94143 0128, USA
J Comput Aided Mol Des 22:269-86. 2008
..Analysis of the changes to the scoring function suggest that modifications can be learned that are related to protein-specific features such as active-site mobility...
- Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery
Universite Paris Diderot, 75013 Paris, France
Drug Discov Today 15:656-67. 2010
Detection, comparison and analyses of binding pockets are pivotal to structure-based drug design endeavors, from hit identification, screening of exosites and de-orphanization of protein functions to the anticipation of specific and non-..
- Structure of a human Tcf4-beta-catenin complex
Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Nat Struct Biol 8:1053-7. 2001
..The structure reveals anticipated similarities with the closely related XTcf3 complex but unexpectedly lacks one component observed in the XTcf3 structure...
- The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design
Rupert J Russell
MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
Nature 443:45-9. 2006
..Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs...
- Drug design against a shifting target: a structural basis for resistance to inhibitors in a variant of influenza virus neuraminidase
J N Varghese
Biomolecular Research Institute 343 Royal Parade, Parkville, 3052, Australia
Structure 6:735-46. 1998
..This study seeks to clarify the structural and functional consequences of replacing the glycerol sidechain of the inhibitor with other chemical constituents...
- Molecule-pharmacophore superpositioning and pattern matching in computational drug design
Inte Ligand GmbH, Mariahilferstrasse 74B 11, 1070 Vienna, Austria
Drug Discov Today 13:23-9. 2008
- Functionalized carbon nanotubes in drug design and discovery
Dipartimento di Scienze Farmaceutiche, Universita di Trieste, 34127 Trieste, Italy
Acc Chem Res 41:60-8. 2008
- Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry
SignalGene Inc, 335 Laird Road, Unit 2, Guelph, Ontario, N1G 4P7, Canada
J Chem Inf Comput Sci 43:218-27. 2003
..It is suggested that by mimicking certain distribution properties of natural compounds, combinatorial products might be made that are substantially more diverse and have greater biological relevance...
- Molecular lipophilicity in protein modeling and drug design
Roman G Efremov
M M Shemyakin and Yu A Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul Miklukho Maklaya, 16 10, Moscow V 437, 117997 GSP, Russia
Curr Med Chem 14:393-415. 2007
..properties of these molecules is indispensable for the development of efficient computational methods in drug design. One possible solution to the problem lies in application of a concept of the 3-dimensional molecular ..
- Definition of the G protein-coupled receptor transmembrane bundle binding pocket and calculation of receptor similarities for drug design
David E Gloriam
Department of Medicinal Chemistry, Pharmaceutical Faculty, Copenhagen University, Universitetsparken 2, 2100 Copenhagen, Denmark
J Med Chem 52:4429-42. 2009
..This has wide applicability to GPCR drug design problems across many disease areas.
- Design of polymeric nanoparticles for biomedical delivery applications
Department of Chemistry, Texas A and M University, P O Box 30012, 3255 TAMU, College Station, Texas 77842 3012, USA
Chem Soc Rev 41:2545-61. 2012
..This tutorial review highlights the importance of well-defined chemistries, with detailed ties to specific biological hurdles and opportunities, in the design of nanostructures for various biomedical delivery applications...
- Computational drug design targeting protein-protein interactions
Rachelle J Bienstock
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Curr Pharm Des 18:1240-54. 2012
..area, can comprise a discontinuous epitope, and is more amorphous and less well defined than the typical drug design target, a small contained enzyme-binding pocket...
- A new drug design targeting the adenosinergic system for Huntington's disease
Nai Kuei Huang
National Research Institute of Chinese Medicine, Taipei, Taiwan
PLoS ONE 6:e20934. 2011
..The expanded CAG repeats are translated into polyglutamine (polyQ), causing aberrant functions as well as aggregate formation of mutant Htt. Effective treatments for HD are yet to be developed...
- Protein-ligand interaction prediction: an improved chemogenomics approach
Mines ParisTech, Centre for Computational Biology, 35 rue Saint Honore, F 77305 Fontainebleau, Institut Curie and INSERM, U900, F 75248, Paris, France
Bioinformatics 24:2149-56. 2008
..However, the accuracy of ligand-based models quickly degrades when the number of known ligands decreases, and in particular the approach is not applicable for orphan receptors with no known ligand...