Computational analysis of binding affinity and neural response at the L-alanine receptor.
J Comput Aided Mol Des
; 9(5): 439-47, 1995 Oct.
Article
en En
| MEDLINE
| ID: mdl-8594161
A model of analogue-receptor binding is developed for the L-alanine receptor in the channel catfish using the AM1-SM2 and ab initio SCRF computational methods. Besides interactions involving the zwitterionic moiety of the amino acid analogue and complementary subsites on the receptor, the model suggests the presence of a hydrophobic pocket with dispersion interactions between the receptor and the residue on the amino acid analogue. Conformational analysis suggests not only a small compact active site on the receptor, but also that the analogues with the highest affinity occupy nearly identical regions of space. Although the binding interaction is dominated by the ionic terms, AM1-SM2 calculations indicate that free energy terms associated with cavity formation, solvent reorganization, and dispersion interactions can be correlated to activation and neural response. From a consideration of this model, molecular features of the analogues that are important for binding and neural response were deduced and other analogues or ligands were developed and tested.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Simulación por Computador
/
Modelos Moleculares
/
Receptores de Aminoácidos
/
Alanina
Límite:
Animals
Idioma:
En
Revista:
J Comput Aided Mol Des
Asunto de la revista:
BIOLOGIA MOLECULAR
/
ENGENHARIA BIOMEDICA
Año:
1995
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Países Bajos