Alkane/Water Partition Coefficient Calculation Based on the Modified AM1 Method and Internal Hydrogen Bonding Sampling Using COSMO-RS
| Autor: | Panagiotis C. Petris, Paul Becherer, Johannes G. E. M. Fraaije |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Materials science
General Chemical Engineering Quantitative Structure-Activity Relationship Thermodynamics Library and Information Sciences 01 natural sciences Article COSMO-RS Alkanes 0103 physical sciences Partition (number theory) Molecule Alkane chemistry.chemical_classification 010304 chemical physics Hydrogen bond Water Charge density Sampling (statistics) Hydrogen Bonding General Chemistry 0104 chemical sciences Computer Science Applications Partition coefficient 010404 medicinal & biomolecular chemistry chemistry Solvents |
| Zdroj: | Journal of Chemical Information and Modeling |
| ISSN: | 1549-960X 1549-9596 |
| DOI: | 10.1021/acs.jcim.0c01478 |
| Popis: | We introduce a physics-based model for calculating partition coefficients of solutes between water and alkanes, using a combination of a semi-empirical method for COSMO charge density calculation and statistical sampling of internal hydrogen bonds (IHBs). We validate the model on the experimental partition data (∼3500 molecules) of small organics, drug-like molecules, and statistical assessment of modeling of proteins and ligand drugs. The model combines two novel algorithms: a bondcorrection method for improving the calculation of COSMO charge density from AM1 calculations and a sampling method to deal with IHBs. From a comparison of simulated and experimental partition coefficients, we find a root-mean-square deviation of roughly one log 10 unit. From IHB analysis, we know that IHBs can be present in two states: open (in water) and closed (in apolar solvent). The difference can lead to a shift of as much as two log 10 units per IHB; not taking this effect into account can lead to substantial errors. The method takes a few minutes of calculation time on a single core, per molecule. Although this is still much slower than quantitative structure−activity relationship, it is much faster than molecular simulations and can be readily incorporated into any screening method. |
| Databáze: | OpenAIRE |
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