Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics

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

SN - 0920-654X

VL - 11

SP - 385

EP - 394

JO - Journal of Computer-Aided Molecular Design

JF - Journal of Computer-Aided Molecular Design

IS - 4

ER -