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Affinity of aporphines for the human 5-HT2A receptor: insights from homology modeling and molecular docking studies.


ABSTRACT: Analogs of nantenine were docked into a modeled structure of the human 5-HT(2A) receptor using ICM Pro, GLIDE, and GOLD docking methods. The resultant docking scores were used to correlate with observed in vitro apparent affinity (K(e)) data. The GOLD docking algorithm when used with a homology model of 5-HT(2A), based on a bovine rhodopsin template and built by the program MODELLER, gives results which are most in agreement with the in vitro results. Further analysis of the docking poses among members of a C1 alkyl series of nantenine analogs, indicate that they bind to the receptor in a similar orientation, but differently than nantenine. Besides an important interaction between the protonated nitrogen of the C1 alkyl analogs and residue Asp155, we identified Ser242, Phe234, and Gly238 as key residues responsible for the affinity of these compounds for the 5-HT(2A) receptor. Specifically, the ability of some of these analogs to establish a H-bond with Ser242 and hydrophobic interactions with Phe234 and Gly238 appears to explain their enhanced affinity as compared to nantenine.

SUBMITTER: Pecic S 

PROVIDER: S-EPMC2918227 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Affinity of aporphines for the human 5-HT2A receptor: insights from homology modeling and molecular docking studies.

Pecic Stevan S   Makkar Pooja P   Chaudhary Sandeep S   Reddy Boojala V BV   Navarro Hernan A HA   Harding Wayne W WW  

Bioorganic & medicinal chemistry 20100620 15


Analogs of nantenine were docked into a modeled structure of the human 5-HT(2A) receptor using ICM Pro, GLIDE, and GOLD docking methods. The resultant docking scores were used to correlate with observed in vitro apparent affinity (K(e)) data. The GOLD docking algorithm when used with a homology model of 5-HT(2A), based on a bovine rhodopsin template and built by the program MODELLER, gives results which are most in agreement with the in vitro results. Further analysis of the docking poses among  ...[more]

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