I'm working in the Carmay Lim
group in the Institute of
Biomedical Sciences and also for the Genomics Research Center at
Academia Sinica Taiwan.
A brief CV is online here
At the moment my research is mainly in the area of protein-protein and protein-DNA insteractions, in particular between Fabs and other protein or peptides. Recent papers have looked at engineered modifications of ColE7 to enable it to bind to different DNA sequences and also papers on why two relativly minor mutations from Ile/Leu to Gly distant from the major binding interface prevented GGPPS from forming dimers. Extensions of this work have led to the DR_Bind DNA binding residue prediction server released in 2012.
Applications of this have been used to probe protein-protein docking via the EMAP module in CHARMM publised in 2013.
For a while I was looking at protein-DNA interactions and in particular mutations of the p53 protein and how they prevent p53 from binding to DNA. It is believed that over 50% of cancers occur because of these mutations. We hope in the long term to design a drug to allow the mutated p53 to bind to DNA and restore its activity. A picture of the wildtype p53 bound to DNA is to the side with the two most frequenty mutated residues in green. Another picture of this solvated and with the counter ions can be found here. The first and second parts of this work has been published in Nucleic Acids Research and The Journal of Physical Chemistry B in 2002.
Before this I studied the interactions of
IgE with the FcR1 receptor and a protein designed by
Tanox Biosystems Inc
to inhibit the binding of IgE and FcR1.
A picture of my current model of the
Ch2 and Ch3 domains of IgE docked to the Tanox Anti-IgE is to the side, this work
has been published in Protein Engineering (1998). In June 2003 the anti-IgE
was accepted by the American Federal Drug Administration for use as an anti-asthma
agent and is now available under the brand name Xolair.
This work is restarting in 2009 with the X-Ray structure of the Xolair FAb being solved and the modelling of full length IgE.
The work is being performed using theoretical means - namely homology modeling, molecular dynamics and protein docking. All the computations are being carried out in house on our Linux based cluster.
As well as my research I also manage the computer systems that the group uses and spend time writing software related to group research. I use Perl scripts and standard UNIX commands such as awk and sed as far as possible. For large projects involving number crunching or graphics I use Fortran90 and the pgplot libraries, for portabilty any parallel codes are written using the Fortran interface to the MPI system.
Previous to working at the Institute of Biomedical Sciences I obtained my Ph.D. working in the
Chris Reynolds group at the
University of Essex, UK and my
B.Sc. from the University of Keele, UK.
My PhD title was Computational Studies of Hypoxia-Selective Bioreductive Agents, and
a pdf version of my thesis can be found online.
An example of this type of agent and its reduction pathway is below: