HOME- Bryn Mawr Conference
- Workshops & Training
- 2010 Oxford (Discovery)
- 2010 Oxford (ADMET)
- 2009 Oxford (Discovery)
- Blanchard, H
- Bryant, S
- Coveney, P
- Hardy, B
- Hawkins, P
- Klamt, A
- Knapp, S
- Kranz, M
- Liebeshuetz, J
- Oledzki, P
- Pirok, G
- Wolber, G
- Zamora, I
- Bursary Award
- 2009 Oxford (ADMET)
- 2008 Oxford
- 2006 Oxford
- Exhibition
- Registration
- Jobs
- Contact
- Support
- Schedule
|
|
|
|
|
|
|
| About Brian Marsden and Stefan Knapp |
|
Brian Marsden is the Principal Investigator in Research Informatics at the Structural Genomics Consortium (SGC) Oxford.
After a degree in Biochemistry at Cambridge, UK, Brian went to Oxford to complete a D.Phil in Biochemistry, focusing on molecular dynamics simulations of extra-cellular modular proteins and their validation by NMR relaxation data. After winning a Wellcome Trust Travelling Research Fellowship, he spent 3 years in the lab of Prof. Ruben Abagyan at the Scripps Research Institute in La Jolla, California learning the tricks of the molecular modelling trade and building large computational clusters.
A move back to the UK found him working as a team leader in Computational Chemistry at BioFocus (now BioFocus DPI, Galapagos) working on the design of ion channel focused small molecule libraries and the development of the Kinase Toolkit.
Brian joined the SGC in 2004 to run the nascent Research Informatics team. Key responsibilities and research areas of this team are IT systems development and support; maintenance of the SGC Oxford target list using advanced bespoke bioinformatics tools; novel methods in public dissemination of structural genomics data (iSee); laboratory information management systems (LIMS) development; computational chemistry and cheminformatics for focussed protein families such as protein kinases and epigenetics-related families. Tools and approaches developed by Brian and his team have been implemented at other SGC nodes as standard.
Brian specialises in protein kinase informatics and computational chemistry in close collaboration with Dr. Stefan Knapp and his team at SGC Oxford.
|
|
Insights into Kinase Structures and Ligand Design
Brian Marsden and Stefan Knapp (University of Oxford)
Structural genomics (SG) has significantly increased the number of novel protein structures of targets with medical relevance. In the protein kinase area, SG has contributed more than 50% of all novel kinase structures during the past four years and determined more than 35 novel catalytic domain structures. This has generated a wealth of freely-available reagents, assays, and inhibitor screening data which may be used for early drug development both in academic labs and in industry.
Kinase structures determined by SG provide enhanced opportunities for structural comparison within sub-families in order to expose novel structural motifs and mechanisms that may play a role in catalytic activity and activation.
Many kinase structures include co-crystallised small molecules which in some cases have exposed novel chemotypes and binding modes. These also include high-resolution structures with well-known inhibitors bound to kinases which they were not originally designed for, giving additional insight into off-pathway interactions.
In this workshop we will provide an overview summary on the current state of structural coverage of the kinome, and will discuss our ideas on how to design selective kinase inhibitors. We will present one of our most recently solved kinase structures whose features the group will visualise, explore and discuss together and which will subsequently be used as a case study during the workshop week.
|
|
|
|
|
|
|
|
|
