The objective of this study was to investigate the conformational and property spaces of acetylcholine in hydrated octanol and in a membrane model. Molecular dynamics simulations of long duration (15 ns) were carried out, yielding 3000 conformers. For each, we calculated N(+)-C8 distance, solvent-accessible surface area (SAS), polar surface area (PSA), dipole moment, and lipophilicity (virtual logP). Their variations as a function of the dihedral angles tau(2) and tau(3) remained unexpectedly broad and comparable to those seen previously in a vacuum, in water, and in chloroform.(12) Thus, each of the seven conformational clusters was able to access a marked proportion of the lipophilicity space accessible to acetylcholine (0.40 in the logP scale). Histograms of logP distributions revealed two overlapping populations, namely more lipophilic and more hydrophilic. Their deconvolution into two Gaussian curves demonstrated solvent-mediated constraints on the lipophilicity space of acetylcholine, clearly showing how a polar medium favors polar conformers, whereas the opposite is true for media of low polarity.
Solvent constraints on the property space of acetylcholine. 2. Ordered media / G. Vistoli, A. Pedretti, L. Villa, B. Testa. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 48:22(2005 May 25), pp. 6926-6935.
|Titolo:||Solvent constraints on the property space of acetylcholine. 2. Ordered media|
VISTOLI, GIULIO (Primo)
PEDRETTI, ALESSANDRO (Secondo)
VILLA, LUIGI (Penultimo)
|Parole Chiave:||conformational space, property space, acetylcholine, virtual logP, lipophilicity|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||25-mag-2005|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/jm0580306|
|Appare nelle tipologie:||01 - Articolo su periodico|