We are developing methods based
mainly on Monte Carlo simulations to address specific problems in structural
biology. We are focusing
mainly on trying to understand structure-dynamics-function relationships in transmembrane
proteins, particularly G-protein coupled receptors (GPCR). GPCR play a
key role in the signaling network inside the cells, comprising about
half of all the targets available for therapeutic drugs in medicine. GPCR regulate many physiological processes,
including: neurotransmission, cell metabolism, cellular growth and differentiation,
immune response, inflammatory processes, taste, smell and vision. One particular
class of GPCR we have been interested in are serotonin receptors, relevant
for understanding the behavioral effects of hallucinogens and for the treatment
of hallucinogen-based syndromes and drug abuse.
A fundamental problem with these systems
is that there is little or no structural information available. Without
knowledge of their structure there is no hope to rationalize their biological
function, let alone to design or improve therapeutic drugs.
Therefore, most of our efforts during
the last years have focused in trying to design protocols to bringing some
structural insight into these very important proteins. However, the design
of searching techniques alone is insufficient to achieve success, and must
be accompanied by continual improvements of the energy function used in
the computational search. This, in turn, requires insight into the physics
of the interactions, as discussed above.
S A Hassan, PhD (main page)