Calculated hydration free energies become less accurate with increases in molecular weight.

ABSTRACT: In order for computer-aided drug design to fulfil its long held promise of delivering new medicines faster and cheaper, extensive development and validation work must be done first. This pertains particularly to molecular dynamics force fields where one important aspect-the hydration free energy (HFE) of small molecules-is often insufficiently analyzed. While most benchmarking studies report excellent accuracies of calculated hydration free energies-usually within 2 kcal/mol of experimental values-we find that deeper analysis reveals significant shortcomings. Herein, we report a dependence of HFE prediction errors on ligand molecular weight-the higher the weight, the bigger the prediction error and the higher the probability the calculated result is erroneous by a large amount. We show tha

SUBMITTER: Ivanov SM 

PROVIDER: S-EPMC11412681 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature