Evaluation of log P, pK a , and log D predictions from the SAMPL7 blind challenge

The Statistical Assessment of Modeling of Proteins and Ligands (SAMPL) challenges focuses the computational modeling community on areas in need of improvement for rational drug design. The SAMPL7 physical property challenge dealt with prediction of octanol-water partition coefficients and pK for 22...

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Veröffentlicht in:Journal of computer-aided molecular design Jg. 35; H. 7; S. 771
Hauptverfasser: Bergazin, Teresa Danielle, Tielker, Nicolas, Zhang, Yingying, Mao, Junjun, Gunner, M R, Francisco, Karol, Ballatore, Carlo, Kast, Stefan M, Mobley, David L
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands 01.07.2021
Schlagworte:
Computational Biology - statistics & numerical data
Computer Simulation - statistics & numerical data
Drug Design - statistics & numerical data
Entropy
Humans
Ligands
Models, Chemical
Models, Statistical
Octanols - chemistry
Quantum Theory
Software - statistics & numerical data
Solubility
Solvents - chemistry
Sulfonamides - chemistry
Sulfonamides - therapeutic use
Thermodynamics
Water - chemistry
pK a
log P
SAMPL
Free energy calculations
ISSN:1573-4951
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Zusammenfassung:The Statistical Assessment of Modeling of Proteins and Ligands (SAMPL) challenges focuses the computational modeling community on areas in need of improvement for rational drug design. The SAMPL7 physical property challenge dealt with prediction of octanol-water partition coefficients and pK for 22 compounds. The dataset was composed of a series of N-acylsulfonamides and related bioisosteres. 17 research groups participated in the log P challenge, submitting 33 blind submissions total. For the pK challenge, 7 different groups participated, submitting 9 blind submissions in total. Overall, the accuracy of octanol-water log P predictions in the SAMPL7 challenge was lower than octanol-water log P predictions in SAMPL6, likely due to a more diverse dataset. Compared to the SAMPL6 pK challenge, accuracy remains unchanged in SAMPL7. Interestingly, here, though macroscopic pK values were often predicted with reasonable accuracy, there was dramatically more disagreement among participants as to which microscopic transitions produced these values (with methods often disagreeing even as to the sign of the free energy change associated with certain transitions), indicating far more work needs to be done on pK prediction methods.
ISSN:1573-4951
DOI:10.1007/s10822-021-00397-3