Simulations Plus, Inc., 42505 10th Street West, Lancaster, CA 93534, USA.
Genentech Inc., Discovery Chemistry, 1 DNA Way, South San Francisco, CA 94080, USA.
Mol Inform. 2024 Oct;43(10):e202400088. doi: 10.1002/minf.202400088. Epub 2024 Jun 21.
In a unique collaboration between Simulations Plus and several industrial partners, we were able to develop a new version 11.0 of the previously published in silico pK model, S+pKa, with considerably improved prediction accuracy. The model's training set was vastly expanded by large amounts of experimental data obtained from F. Hoffmann-La Roche AG, Genentech Inc., and the Crop Science division of Bayer AG. The previous v7.0 of S+pKa was trained on data from public sources and the Pharmaceutical division of Bayer AG. The model has shown dramatic improvements in predictive accuracy when externally validated on three new contributor compound sets. Less expected was v11.0's improvement in prediction on new compounds developed at Bayer Pharma after v7.0 was released (2013-2023), even without contributing additional data to v11.0. We illustrate chemical space coverage by chemistries encountered in the five domains, public and industrial, outline model construction, and discuss factors contributing to model's success.
在 Simulations Plus 与几家工业合作伙伴之间的独特合作下，我们成功地开发了之前发表的计算机模拟 pK 模型 S+pKa 的新版本 11.0，其预测准确性有了显著提高。该模型的训练集通过从罗氏公司、基因泰克公司和拜耳作物科学部门获得的大量实验数据得到了极大的扩展。之前的 S+pKa v7.0 是基于来自公共资源和拜耳制药部门的数据进行训练的。该模型在对三个新贡献化合物集进行外部验证时，在预测准确性方面显示出了显著的提高。出乎意料的是，在 v7.0（2013-2023 年）发布后，即使没有向 v11.0 提供额外的数据，v11.0 也提高了对拜耳制药公司开发的新化合物的预测能力。我们通过在五个领域（公共和工业）中遇到的化学物质来说明化学空间覆盖范围，概述模型构建，并讨论促成模型成功的因素。
