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SAMPL7 physical property prediction from EC-RISM theory.

ABSTRACT: Inspired by the successful application of the embedded cluster reference interaction site model (EC-RISM), a combination of quantum-mechanical calculations with three-dimensional RISM theory to predict Gibbs energies of species in solution within the SAMPL6.1 (acidity constants, pK_a) and SAMPL6.2 (octanol-water partition coefficients, log P) the methodology was applied to the recent SAMPL7 physical property challenge on aqueous pK_a and octanol-water log P values. Not part of the challenge but provided by the organizers, we also computed distribution coefficients log D_7.4 from predicted pK_a and log P data. While macroscopic pK_a predictions compared very favorably with experimental data (root mean square error, RMSE 0.72 pK units), the performance of the log P model (RMSE 1.84) fell behind expectations from the SAMPL6.2 challenge, leading to reasonable log D_7.4 predictions (RMSE 1.69) from combining the independent calculations. In the post-submission phase, conformations generated by different methodology yielded results that did not significantly improve the original predictions. While overall satisfactory compared to previous log D challenges, the predicted data suggest that further effort is needed for optimizing the robustness of the partition coefficient model within EC-RISM calculations and for shaping the agreement between experimental conditions and the corresponding model description.

SUBMITTER: Tielker N

PROVIDER: S-EPMC8367877 | biostudies-literature |

REPOSITORIES: biostudies-literature

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