Zhao Shiji, Cieplak Piotr, Duan Yong, Luo Ray
Nurix Therapeutics, Inc., 1700 Owens Street Suite 205, San Francisco, California 94158, United States.
SBP Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, United States.
J Chem Theory Comput. 2024 Mar 12;20(5):2098-2110. doi: 10.1021/acs.jctc.3c01347. Epub 2024 Feb 23.
Accurate parametrization of amino acids is pivotal for the development of reliable force fields for molecular modeling of biomolecules such as proteins. This study aims to assess amino acid electrostatic parametrizations with the polarizable Gaussian Multipole (pGM) model by evaluating the performance of the pGM-perm (with atomic permanent dipoles) and pGM-ind (without atomic permanent dipoles) variants compared to the traditional RESP model. The 100-conf-combterm fitting strategy on tetrapeptides was adopted, in which (1) all peptide bond atoms (-CO-NH-) share identical set of parameters and (2) the total charges of the two terminal -acetyl (ACE) and -methylamide (NME) groups were set to neutral. The accuracy and transferability of electrostatic parameters across peptides with varying lengths and real-world examples were examined. The results demonstrate the enhanced performance of the pGM-perm model in accurately representing the electrostatic properties of amino acids. This insight underscores the potential of the pGM-perm model and the 100-conf-combterm strategy for the future development of the pGM force field.
氨基酸的精确参数化对于开发用于蛋白质等生物分子分子建模的可靠力场至关重要。本研究旨在通过评估与传统RESP模型相比，具有可极化高斯多极子（pGM）模型的pGM-perm（带有原子永久偶极）和pGM-ind（不带有原子永久偶极）变体的性能，来评估氨基酸静电参数化。采用了对四肽的100-构象-组合项拟合策略，其中（1）所有肽键原子（-CO-NH-）共享相同的参数集，并且（2）两个末端-乙酰基（ACE）和-甲酰胺基（NME）基团的总电荷设为中性。研究了静电参数在不同长度肽和实际例子中的准确性和转移性。结果表明，pGM-perm模型在准确表示氨基酸静电性质方面具有增强的性能。这一见解突出了pGM-perm模型和100-构象-组合项策略在pGM力场未来发展中的潜力。
