Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics
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Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics. / Christensen, I T; Jørgensen, Flemming Steen.
In: Journal of Computer - Aided Molecular Design, Vol. 11, No. 4, 1997, p. 385-94.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics
AU - Christensen, I T
AU - Jørgensen, Flemming Steen
PY - 1997
Y1 - 1997
N2 - A molecular dynamics (MD)-based conformational analysis has been performed on a number of cycloalkanes in order to demonstrate the reliability and generality of MD as a tool for conformational analysis. MD simulations on cyclohexane and a series of methyl-substituted cyclohexanes were performed at temperatures between 400 and 1200 K. Depending on the simulation temperature, different types of interconversions (twist-boat-twist-boat, twist-boat-chair and chair-chair) could be observed, and the MD simulations demonstrated the expected correlation between simulation temperature and ring inversion barriers. A series of methyl-substituted 1,3-dioxanes were investigated at 1000 K, and the number of chair-chair interconversions could be quantitatively correlated to the experimentally determined ring inversion barrier. Similarly, the distribution of sampled minimum-energy conformations correlated with the energy-derived Boltzmann distribution. The macrocyclic ring system cyclododecane was subjected to an MD simulation at 1000 K and 71 different conformations could be sampled. These conformations were compared with the results of previously reported conformational analyses using stochastic search methods, and the MD method provided 19 out of the 20 most stable conformations found in the MM2 force field. Finally, the general performance of the MD method for conformational analysis is discussed.
AB - A molecular dynamics (MD)-based conformational analysis has been performed on a number of cycloalkanes in order to demonstrate the reliability and generality of MD as a tool for conformational analysis. MD simulations on cyclohexane and a series of methyl-substituted cyclohexanes were performed at temperatures between 400 and 1200 K. Depending on the simulation temperature, different types of interconversions (twist-boat-twist-boat, twist-boat-chair and chair-chair) could be observed, and the MD simulations demonstrated the expected correlation between simulation temperature and ring inversion barriers. A series of methyl-substituted 1,3-dioxanes were investigated at 1000 K, and the number of chair-chair interconversions could be quantitatively correlated to the experimentally determined ring inversion barrier. Similarly, the distribution of sampled minimum-energy conformations correlated with the energy-derived Boltzmann distribution. The macrocyclic ring system cyclododecane was subjected to an MD simulation at 1000 K and 71 different conformations could be sampled. These conformations were compared with the results of previously reported conformational analyses using stochastic search methods, and the MD method provided 19 out of the 20 most stable conformations found in the MM2 force field. Finally, the general performance of the MD method for conformational analysis is discussed.
KW - Calorimetry
KW - Cyclohexanes
KW - Dioxanes
KW - Models, Molecular
KW - Molecular Conformation
KW - Molecular Structure
KW - Reproducibility of Results
KW - Software
KW - Structure-Activity Relationship
U2 - 10.1023/A:1007925123923
DO - 10.1023/A:1007925123923
M3 - Journal article
C2 - 9334904
VL - 11
SP - 385
EP - 394
JO - Journal of Computer-Aided Molecular Design
JF - Journal of Computer-Aided Molecular Design
SN - 0920-654X
IS - 4
ER -
ID: 38394410