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

Estimating Atomic Contributions to Hydration and Binding using Free Energy Perturbation
Benedict W. J. Irwin, David John Huggins
Journal of Chemical Theory and Computation

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

Computational Fluorine Scanning Using Free-Energy Perturbation
Alexander D Wade, Andrea Rizzi, Yuanqing Wang, and David J Huggins
Journal of Chemical Information and Modeling

Overcoming Chemical, Biological, and Computational Challenges in the Development of Inhibitors Targeting Protein-Protein Interactions
Luca Laraia, Grahame McKenzie, David R Spring, Ashok R Venkitaraman, David J Huggins
Chemistry & Biology - 2015

Design, Synthesis, and Biological and Structural Evaluations of Novel HIV-1 Protease Inhibitors To Combat Drug Resistance
Maloy Kumar Parai, David J Huggins, Hong Cao, Madhavi NL Nalam, Akbar Ali, Celia A Schiffer, Bruce Tidor, Tariq M Rana
Journal of Medicinal Chemistry - 2012, Volume 55: Issue 14

Rational Approaches to Improving Selectivity in Drug Design
David J. Huggins, Woody Sherman, and Bruce Tidor
Journal of Medicinal Chemistry - 2012 , Volume 55: Issue 4

Evaluation of an Inverse Molecular Design Algorithm in a Model Binding Site
David J. Huggins, Michael Altman, Bruce Tidor
Proteins: Structure, Function and Bioinformatics - 2009, Volume 75: Issue 1

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

Optimization of Protein-Ligand Electrostatic Interactions Using An Alchemical Free-Energy Method
Alexander D Wade and David J Huggins
Journal of Chemical Theory and Computation

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
Collaborators
University of Cambridge
University of Cambridge
Cambridge
University of Newcastle
Massachusetts Institute of Technology
London
University of Cambridge
