期刊
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
卷 17, 期 7, 页码 3908-3915出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jctc.1c00219
关键词
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资金
- National Natural Science Foundation of China [22073050, 21775076]
- Natural Science Foundation of Tianjin, China [20JCYBJC01480]
- Fundamental Research Funds for the Central Universities, Nankai University [63211019, 63201015]
- China Postdoctoral Science Foundation [bs6619012]
- Agence Nationale de la Recherche
Modifying Lennard-Jones parameters and utilizing NBFIX corrections in the CHARMM36 force field significantly improves the description of protein-ligand complexes, especially those involving cation-pi interactions. Results show that the optimized CHARMM36m-NBF and CHARMM36-WYF parameters provide more accurate binding free energy calculations compared to the original force fields.
Modifying pair-specific Lennard-Jones parameters through the nonbonded FIX (NBFIX) feature of the CHARMM36 force field has proven cost-effective for improving the description of cation-pi interactions in biological objects by means of pairwise additive potential energy functions. Here, two sets of newly optimized CHARMM36 force-field parameters including NBFIX corrections, coined CHARMM36m-NBF and CHARMM36-WYF, and the original force fields, namely CHARMM36m and Amber ff14SB, are used to determine the standard binding free energies of seven protein-ligand complexes containing cation-pi interactions. Compared with precise experimental measurements, our results indicate that the uncorrected, original force fields significantly underestimate the binding free energies, with a mean error of 5.3 kcal/mol, while the mean errors of CHARMM36m-NBF and CHARMM36-WYF amount to 0.8 and 2.1 kcal/mol, respectively. The present study cogently demonstrates that the use of modified parameters jointly with NBFIX corrections dramatically increases the accuracy of the standard binding free energy of protein-ligand complexes dominated by cation-pi interactions, most notably with CHARMM36m-NBF.
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