Solvent-Dependent Conformational Studies of Acetylcholine and Some Related Molecules

Weintraub, Herschel J. R.; Hopfinger, A. J.

doi:10.1007/978-94-010-1758-9_11

Cited by 8 publications

(9 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A total of 1369 frames were optimized, giving rise to a potential-energy map ( Fig. 1) very similar to those previously drawn employing dierent force ®elds [4,9,16,17].…”

Section: Resultsmentioning

confidence: 94%

Molecular dynamics, density functional and second-order Møller-Plesset theory study of the structure and conformation of acetylcholine in vacuo and in solution

Marino

Russo

Tocci

et al. 2001

Theoretical Chemistry Accounts: Theory, Computation, and Modeli

View full text Add to dashboard Cite

Molecular mechanics minimizations based on the CVFF force ®eld and molecular dynamics simulation for a time of 2.5 ns were performed to examine the conformational behaviour and the molecular motion of acetylcholine in vacuo and in aqueous solution. Five low-lying conformations, namely the TT, TG, GG, G*G and GT, were obtained from molecular mechanics computations with the GT structure as the absolute minimum. Molecular dynamics trajectories in vacuo and in water show that only four (GT, GG, G*G and TG) and three (TG, TT and GT) conformations are present in the simulation time, respectively. Density functional B3LYP and second-order Mùller± Plesset (MP2) methods were then used to study all the ®ve lowest-lying conformers of acetylcholine neurotransmitter in vacuo and in water by the polarizable continuum model approach. The B3LYP and MP2 computations show that in the gas phase all minima lie in a narrow range of energy with the G*G conformer as the most stable one. The relative minima GG, GT, TG and TT are located at 1.1 (3.3), 1.8 (4.2), 2.1 (4.5) and 4.3 (7.3) kcal/mol above the absolute one at the B3LYP (MP2) level. The preferred conformation in water is the TG. Solvation reduces the relative energy dierences between the ®ve minima in both computations.

show abstract

“…A total of 1369 frames were optimized, giving rise to a potential-energy map ( Fig. 1) very similar to those previously drawn employing dierent force ®elds [4,9,16,17].…”

Section: Resultsmentioning

confidence: 94%

Molecular dynamics, density functional and second-order Møller-Plesset theory study of the structure and conformation of acetylcholine in vacuo and in solution

Marino

Russo

Tocci

et al. 2001

Theoretical Chemistry Accounts: Theory, Computation, and Modeli

View full text Add to dashboard Cite

show abstract

“…To understand the interactions of biologically interesting molecules, it is necessary to know the shape of the interaction sites as well as the conformations of the interacting molecules and, the conformational analysis of Ach has been subject of many experimental 6–25 and theoretical 26–46 investigations. Aspects of the Ach potential energy surface (PES) have been the subject of numerous experimental investigations including X‐Ray 6–8, 16–21, NMR 9, 11–14, 23, 25, electron diffraction 22, and Raman Spectroscopy 15, in addition, computational studies have employed ab initio 3, 31, 34, 35, 42–44, semi empirical and empirical methods 26–30, 38, 39 as well as molecular dynamics 36, 37, 45.…”

Section: Introductionmentioning

confidence: 99%

A DFT study of determination of the reactive sites of the acetylcholine and its agonists: In the gas phase and dielectric medium

Serdaroğlu

2011

Int J of Quantum Chemistry

View full text Add to dashboard Cite

The reactive behavior of acetylcholine and its agonist molecules have been investigated using B3LYP hybrid density functional method at the 6-311þþG** basis set level, in the gas phase and aqueous phase. The calculations have been performed to obtain optimized geometries, relative reactivities, net atomic charges, HOMO, and LUMO energies. The solvent effect has been analyzed by using the continuum model (IPCM) and, the obtained results have shown that the all molecules have been stabilized more by solvent dielectric constant. For Ach and its analogues, it has been very well known that esteratic site and quaternary ammonium group which have reflected the difference in biological activity have been the two of the most important active site for interactions between molecule and its receptor. The structures of these analogues have provided an essential foundation for subsequent structureactivity analysis of ligand binding at acetylcholine receptors, neuronal uptake inhibitors and transporters. Molecular modeling predictions will be important initial steps toward the development of novel pharmaceuticals in the fight acetylcholine-related neurological disorders. This work is therefore expected to facilitate the design and development of new biologically active Ach analogues to treat Ach-related neurological disorders and, specially is used to qualitative understanding of the reactivity and related properties and, so on can be used to a preselection of new ligands which at the moment is taken essentially from empirical knowledge. V

show abstract

“…Two of these, C 4 N 1 C 5 C 6 and C 6 O 7 C 8 C 10 , are found to be trans in most of the previous experimental and theoretical studies. [11][12][13][30][31][32][38][39][40][41] The remaining torsions N 1 C 5 C 6 O 7 and C 5 C 6 O 7 C 8 are used to describe the conformational flexibility of ACh. In the gas phase, each of these rotation angles can be trans (t, ∼180°), gauche (g, ∼120°), or gauche′ (g′, ∼ -120°).…”

Section: Introductionmentioning

confidence: 99%

“…19 Computational studies have employed ab initio, 2,35,[38][39][48][49][50] semiempirical, and empirical methods, [30][31][32][33][34][42][43][44][45] as well as molecular dynamics. [40][41]52 However, despite the large number of reported works, several issues remain unresolved.…”

Section: Introductionmentioning

confidence: 99%

“…Aspects of the ACh potential energy surface (PES) have been the subject of numerous experimental investigations, including X-ray, [10][11][12][20][21][22][23][24][25] NMR, 13,[15][16][17][18]27,29 electron diffraction, 26 and Raman spectroscopy. 19 Computational studies have employed ab initio, 2,35,[38][39][48][49][50] semiempirical, and empirical methods, [30][31][32][33][34][42][43][44][45] as well as molecular dynamics. [40][41]52 However, despite the large number of reported works, several issues remain unresolved.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Theoretical Investigations of Acetylcholine (ACh) and Acetylthiocholine (ATCh) Using ab Initio and Effective Fragment Potential Methods

et al. 2004

View full text Add to dashboard Cite

Both the effective fragment potential method and fully ab initio HF and MP2 methods have been used to study solvation effects on the conformational potential energy surfaces of ACh and ATCh. Comparisons of hydrated geometries and relative energies show that EFP1 can generate results quite close to the much more time-consuming ab initio calculations. Hydrated structures of ACh and ATCh prefer bridged water structures. Very limited effects from the solvation have been observed in ACh and ATCh. In both the gas and aqueous solution, ACh prefers the gauche NCCO arrangement, whereas ATCh favors trans NCCS. Possible interpretations are discussed. Disciplines Chemistry CommentsReprinted (adapted) Both the effective fragment potential method and fully ab initio HF and MP2 methods have been used to study solvation effects on the conformational potential energy surfaces of ACh and ATCh. Comparisons of hydrated geometries and relative energies show that EFP1 can generate results quite close to the much more time-consuming ab initio calculations. Hydrated structures of ACh and ATCh prefer bridged water structures. Very limited effects from the solvation have been observed in ACh and ATCh. In both the gas and aqueous solution, ACh prefers the gauche NCCO arrangement, whereas ATCh favors trans NCCS. Possible interpretations are discussed.

show abstract

Solvent-Dependent Conformational Studies of Acetylcholine and Some Related Molecules

Cited by 8 publications

References 6 publications

Molecular dynamics, density functional and second-order Møller-Plesset theory study of the structure and conformation of acetylcholine in vacuo and in solution

Molecular dynamics, density functional and second-order Møller-Plesset theory study of the structure and conformation of acetylcholine in vacuo and in solution

A DFT study of determination of the reactive sites of the acetylcholine and its agonists: In the gas phase and dielectric medium

Theoretical Investigations of Acetylcholine (ACh) and Acetylthiocholine (ATCh) Using ab Initio and Effective Fragment Potential Methods

Contact Info

Product

Resources

About