Development of ion channels activity ranking techniques on example of voltage gated potassium channel
Stockholm Bioinformatics Center Seminars
Wednesday 16 June 2010
to 17:00 at
Wiktor Jurkowski (SBC)
Ion channels and transporters are crucial for the generation, propagation and inter-synaptic conduction of nerve impulses and therefore important drug target related to many malfunctions of the central and peripheral neural system. Because of its specific structural properties standard structure based drug design approach trained on soluble globular enzymes cannot be directly applied. One exemplary problem which has to be addressed is the reliability of the scoring functions in correct ranking of active and inactive binders which consequently is necessary to e.g. elucidate new lead structures.
Multiple virtual screening techniques have been tested in terms of applicability to correctly rank the ligand libraries of known activities. We found that combination of multiple approaches can yield better enrichments and hence be more efficient in ligand classification.
It is clear that there is no one unique mechanism of voltage gated potassium channel blocking. The receptor can be targeted in the central pore or in the voltage sensing domain. I will present various ligand - receptor interacting hypotheses and possible use of them in development of target specific hits.