Models Based on MD Calculations

MD simulations in expHcit solvents are stiU beyond the scope of the current computational power for screening of a large number of molecules. However, mining powerful quantum chemical parameters to predict log P via this approach remains a challenging task. QikProp [42] is based on a study [3] which used Monte Carlo simulations to calculate 11 parameters, including solute-solvent energies, solute dipole moment, number of solute-solvent interactions at different cutoff values, number of H-bond donors and acceptors (HBDN and HBAQ and some of their variations. These parameters made it possible to estimate a number of free energies of solvation of chemicals in hexadecane, octanol, water as well as octanol-water distribution coefficients. The equation calculated for the octanol-water coefficient is  

QikProp does not perform MD simulahons but calculates required parameters from supplied 3D structures of molecules. For example, it computes atomic charges using the semi-empirical CM Ip method, ASA is calculated using a 1.4 A probe radius [43]. The recent parameters of QikProp were optimized using 500 drugs and related heterocyclic compounds and the model calculated an of 0.93 and an RMSE of 0.49 for more than 400 drug-like compounds [42]. 

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