Computational Drug Discovery

Recommended Prerequisites

Not applicable.

Teaching Methods

Expositive classes and seminars delivered by specialists with students interaction according to what is expected at the PhD level.

Learning Outcomes

 

Exposes the students to the state-of-the-art computational tools used in ligand- and target-based drug design, pharmacophore modeling, virtual screening, fragment-based design, 3D-QSAR, and de novo design.

Work Placement(s)

No

Syllabus

1. Exploring structure-activity relationships

2. Computational modeling and design

3. Chemometrics and molecular simulation

4. Hit- and Lead-Compound Discovery.

Head Lecturer(s)

Rui Manuel Pontes Meireles Ferreira de Brito

Assessment Methods

Assessment
Written report: 100.0%

Bibliography

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Sliwoski G, Kothiwale S, Meiler J, Lowe EW Jr., Computational methods in drug discovery, Pharmacol Rev. 2013, 66, 334-95. doi: 10.1124/pr.112.007336

Hanna Geppert, Martin Vogt, and Jurgen Bajorath, Current Trends in Ligand-Based Virtual Screening: Molecular Representations, Data Mining Methods, New Application Areas, and Performance Evaluation, J. Chem. Inf. Model. 2010, 50, 205–216.

Areias, L. R. P., Ruivo, E. F. P., Goncalves, L. M., Duarte, M. T., Andre, V., Moreira, R., Lucas, S. D., Guedes, R. C., “A unified approach toward the rational design of selective low nanomolar human neutrophil elastase inhibitors” " RSC ADVANCES, 2015, 5, 51717-51721

Lucas, S. D., Gonçalves, L. M., Carvalho, L. A. R., Correia, H. F., da Costa, E. M. R.,Guedes, R. A., Moreira, R., Guedes, R. C., "Optimization of O3-Acyl Kojic Acid Derivatives as Potent and Selective Human Neutrophil Elastase Inhibitors", J. Med. Chem., 2013, 56, 9802-6.

DOI: 10.1021/jm4011725

Mugumbate, G., Newton, A. S., Rosenthal, P. J., Gut, J., Moreira, R., Chibale, K. and Guedes, R. C. “Novel anti-Plasmodial leads identified by virtual screening of the ZINC database”, Journal of Computer-Aided Molecular Design, 2013, 27, 859-871.

DOI: 10.1007/s10822-013-9685-z

Jitender Verma, Vijay M. Khedkar and Evans C. Coutinho, 3D-QSAR in Drug Design - A Review, Current Top. Med. Chem., 2010, 10, 95-115.

http://dx.doi.org/10.2174/156802610790232260

Carolina H. Andrade, Kerly F. M. Pasqualoto, Elizabeth I. Ferreira and Anton J. Hopfinger, 4D-QSAR: Perspectives in Drug Design, Molecules, 2010, 15, 3281-3294.

http://dx.doi.org/10.3390/molecules15053281

Hans-Dieter Höltje, Wolfgang Sippl, Didier Rognan and Gerd Folkers, Molecular Modeling; Wiley-VCH; 3 edition (February 26, 2008).

A.R. Leach, Molecular Modelling: Principles and Applications; Prentice Hall 2nd (second) (2001)

David C. Young Computational drug design, Wiley-Interscience; 1 edition (February 12, 2009)

Lavecchia, A. and Di Giovanni, C., Virtual Screening Strategies in Drug Discovery: A Critical Review, Current Medicinal Chemistry 2013, 20,  2839-2860.

Artem Cherkasov et al, QSAR Modeling: Where Have You Been? Where Are You Going To?, J. Med. Chem. 2014, 57, 4977-5010 dx.doi.org/10.1021/jm4004285

Carlos J. V. Simoes, Trishna Mukherjee, Rui M. M. Brito, and Richard M. Jackson, Toward the Discovery of Functional Transthyretin Amyloid Inhibitors: Application of Virtual Screening Methods, J. Chem. Inf. Model. 2010, 50, 1806–1820. doi: 10.1021/ci100250z

Lucas, S. D., Gonçalves, L. M., Cardote, T. A., Correia, H. F., Moreira, R., Guedes, R. C., “Structure based virtual screening for discovery of novel human neutrophil elastase inhibitors”, Med. Chem. Commun, 2012, 3, 1299-1304.

DOI: 10.1039/C2MD20090B

A.R. Leach, Molecular Modelling: Principles and Applications (2nd Edition), Pearson (Harlow, UK, 2001)

D.C. Rapaport, The art of molecular dynamics simulation (2nd Edition), Cambridge (Cambridge, 2004)

G.A. Lewis, D. Mathieu, R. Phan-Tan-Luu, Pharmaceutical Experimental Design, Dekker (New York, 1999)

C.S. Vitorino et al, Co-encapsulating nanostructured lipid carriers for transdermal application: From experimental design to the molecular detail, J. Control. Release, 167, 301-314 (2013 )