Molecular Design For Drug Discovery

Computational molecular design is a useful tool in modern drug discovery. Virtual screening is an approach that evaluates individual members of compound libraries. In contrast, design approaches construct compounds by combining scaffolds and sidegroups to optimise the calculated binding affinity. We develop software tools and apply molecular design to drug discovery projects.


Publications

Computationally-Guided Optimization of Small-Molecule Inhibitors of the Aurora A Kinase – TPX2 Protein-Protein Interaction

Daniel Cole,  Matej Janecek,  Jamie Stokes,  Maxim Rossmann,  John Faver,  Grahame McKenzie,  Ashok Venkitaraman,  Marko Hyvönen,  David R Spring,  David John Huggins  and  WL Jorgensen

Chemical Communications

Biomolecular simulations: From dynamics and mechanisms to computational assays of biological activity

David J. Huggins, Philip C. Biggin, Marc A. Dämgen, Jonathan W. Essex, Sarah A. Harris, Richard H. Henchman, Syma Khalid, Antonija Kuzmanic, Charles A. Laughton, Julien Michel, Adrian J. Mulholland, Edina Rosta, Mark S. P. Sansom, Marc W. van der Kamp

Wiley Interdisciplinary Reviews: Computational Molecular Science

Modulating Protein-Protein Interactions of the Mitotic Polo-like Kinases to Target Mutant KRAS

Ana J. Narvaez, Suzan Ber, Alex Crooks, Amy Emery, Bryn Hardwick, Estrella Guarino Almeida, David J. Huggins, David Perera, Meredith Roberts-Thomson, Roberta Azzarelli, Fiona E. Hood, Ian A. Prior, David W. Walker, Richard Boyce, Robert G. Boyle, Samuel P. Barker, Christopher J. Torrance, Grahame J. McKenzie, Ashok R. Venkitaraman

Cell Chemical Biology

Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2

Matej Janecek, Maxim Rossmann, Pooja Sharma, Amy Emery, David J Huggins, Simon R Stockwell, Jamie E Stokes, Yaw S Tan, Estrella Guarino Almeida, Bryn Hardwick, Ana J Narvaez, Marko Hyvönen, David R Spring, Grahame J McKenzie, Ashok R Venkitaraman

Scientific Reports - 2016

Inhibition of 3-Phosphoglycerate Dehydrogenase (PHGDH) by Indole Amides Abrogates de novo Serine Synthesis in Cancer Cells

Edouard Mullarky, Jiayi Xu, Anita Robin, David Huggins, Andy Jennings, Naoyoshi Noguchi, Michael Miller, Nigel Liverton, Daisuke Tomita, Mayako Michino, Taojunfeng Su, Guoan Zhang, Andy Stamford, Peter Meinke, Stacia Kargman and Lewis C. Cantley

Bioorganic & Medicinal Chemistry Letters

A cryptic hydrophobic pocket in the polo-box domain of the polo-like kinase PLK1 regulates substrate recognition and mitotic chromosome segregation

Pooja Sharma, Robert Mahen, Maxim Rossmann, Jamie E. Stokes, Bryn Hardwick, David J. Huggins, Amy Emery, Dominique L. Kunciw, Marko Hyvönen, David R. Spring, Grahame J. McKenzie & Ashok R. Venkitaraman

 

https://www.nature.com/articles/s41598-019-50702-2

Scientific Reports

© 2019 Theory of Condensed Matter Group, Cavendish Laboratory, JJ Thomson Avenue, Cambridge, CB3 0HE, United Kingdom