Approaches to molecular modeling studies and specific application to serotonin ligands and receptors.
Molecular modeling studies are useful in as much as they may allow us to understand the activity and selectivity of currently existing agents, and, furthermore, may aid in the design of completely novel therapeutic agents. There are two basic modeling strategies: the ligand-ligand approach and the ligand-receptor approach. Both approaches possess certain inherent advantages and disadvantages and, in addition, make certain assumptions about the agents and/or receptors being investigated. Keeping with the spirit of this minisymposium, we describe these two approaches, their general usefulness, and their limitations. Using serotonin (5-HT) receptors as a focal point, we review and provide novel examples of molecular modeling studies involving both strategies. Presented for the first time are examples of ligand-receptor models to account for the binding of serotonergic agents at 5-HT2 and 5-HT1C receptors.
Westkaemper
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RB
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Glennon
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
D008024:Ligands; D011985:Receptors, Serotonin