Conformational flexibility and receptor interaction.
This theoretical analysis shows that the experimentally observed standard Gibbs free energy of binding of a ligand by a receptor can be described by two terms. One term describes the free energy of binding of the drug to the receptor when both are in their lowest energy conformation. The second term gives the difference between the average and the lowest conformational energy of the two species involved. It also follows that all drug molecules having an energy higher than the minimum energy, must have a higher affinity than molecules occurring in the minimum energy conformation, independent of the energy level of the receptor bound conformation.
Department of Medicinal Chemistry, Faculty of Pharmacy, Universiteit Utrecht, The Netherlands. l.h.m.janssen@far.ruu.nl
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D007650:Ketanserin / Q000737:chemistry; D008024:Ligands; D008968:Molecular Conformation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000737:chemistry; D013816:Thermodynamics
D008024:Ligands; D011506:Proteins; D012702:Serotonin Antagonists; D007650:Ketanserin