DRUG DISCOVERY INTERFACE: Functional Group Dependence of Solute Partitioning to Various Locations within a DOPC Bilayer: A Comparison of Molecular Dynamics Simulations with Experiment

Predicting solute partitioning in lipid bilayers: Free energies and partition coefficients from molecular dynamics simulations and COSMOmic

“…Assuming that the membrane center can be modeled by cyclohexane, 32 the MD result shows a better prediction for 4-ethylphenol at the membrane center. The free energy profile of 4-ethylphenol in a DOPC membrane of another MD study 24 deviates from the calculations in this work as a minimum free energy of ∼ −26 kJ/mol was reported (see also Sec. III B).…”

“…With a logK (b, c) value of around 2.8, 4-ethylphenol is mainly located in the membrane. By comparing free energies of transfer, Tejwani et al 24 showed that their MD results for 4-ethylphenol are not in quantitative agreement with experimental data. Using their free energy profile to calculate a partition coefficient leads to logK (b, c) ≈ 4.1, thus overpredicting the experimental results by 1.3 log units and deviating from our MD result (see Table II).…”

“…23,32 Others have transferred experimental partition coefficients into a free energy of partitioning and compared them to transfer energies deduced from calculated free energy profiles. 11,16,24,35 Only a few authors calculated partition coefficients from simulated free energy profiles and compared them to experimental data. 20,26 Terama et al 43 calculated partition coefficients from equilibrium MD simulations.…”

Permeability of Fluid-Phase Phospholipid Bilayers: Assessment and Useful Correlations for Permeability Screening and Other Applications

“…Its resolution lies in a more detailed consideration of molecular-and atomic-scale permeant-bilayer interactions. Analyses of chemical group contributions to the overall free energy of permeant-bilayer interaction by Xiang, Anderson, and coworkers 28,29,[33][34][35]50,86,94,105 represent an important step in this direction, as do numerous computer simulation studies cited above.…”

The errors of our ways: taking account of error in computer-aided drug design to build confidence intervals for our next 25 years

“…I'm certainly no stranger to using force fields and I'm regularly impressed by how well force fields can duplicate the structure and conformation of isolated small molecules in vacuo, having routinely compared a number of different force fields to experimentally and quantum mechanically determined structures. Additionally, I marvel at how well force field driven molecular dynamics (MD) simulation can duplicate and maintain biological systems, including highly fluid lipid bilayers [18,19]. My assumption is that they work so well partly because once atoms are connected by the strong bond stretching and angle bending forces, there are only so many ways to pack connected balls together in a box.…”