Computer-Aided Chemical Biology

The development of publically-available chemical probes for the purpose of target exploration is a new paradigm in drug discovery. This shift has been pioneered by non-profit and open-source ventures such as the SGC and NIH chemical probes.

Having publically available chemical probes for potential drug targets facilitates an open assessment of target viability, paving the way for commercial ventures to develop effective treatments at a lower societal cost. We are applying computational methods such as alchemical free-energy calculation to the development of chemical probes for the purpose of target validation.

The main advantages of these computational methods are that they can analyse multiple structures using a very large number of potential chemical elaborations and identify surprising and sometimes counter-intuitive successes.


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

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

PARP1- dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair

Hanan Khoury-Haddad, Noga Guttmann-Raviv, Inbal Ipenberg, David Huggins, Anand D. Jeyasekharan, and Nabieh Ayoub

PNAS - 2014

Characterization and tissue-specific expression of two lepidopteran farnesyl diphosphate synthase homologs: implications for the biosynthesis of ethyl-substituted juvenile hormones

Michel Cusson, Catherine Beliveau, Stephanie E. Sen, Sophie Vandermoten, Robert G. Rutledge, Don Stewart, Frederic Francis, Eric Haubruge, Peter Rehse, David J. Huggins, Guy H. Grant

Proteins: Structure, Function and Bioinformatics - 2006, Volume 65: Issue 3

A role for glycine in the gating of plant NMDA-like receptors

Christian Dubos, David Huggins, Guy H. Grant, Marc R. Knight, Malcolm M. Campbell.

The Plant Journal - 2003, Volume 35: Issue 6

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

Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand

Cai ReadDuuamene NyimanuThomas L. WilliamsDavid J. HugginsPetra SulenticRobyn G. C. MacraePeiran YangRobert C. GlenJanet J. Maguire and Anthony P. Davenport

Pharmacological Reviews

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 and Ashok R. Venkitaraman

Scientific Reports

Development of a Novel Cell-Permeable Protein–Protein Interaction Inhibitor for the Polo-box Domain of Polo-like Kinase 1

David J. Huggins, Bryn S. Hardwick, Pooja Sharma, Amy Emery, Luca Laraia, Fengzhi Zhang, Ana J. Narvaez, Meredith Roberts-Thomson, Alex T. Crooks. Robert G. Boyle, Richard Boyce, David W. Walker, Natalia Mateu, Grahame J. McKenzie, David R. Spring, and Ashok R. Venkitaraman

ACS Omega

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