Developing Quantum Chemical Topology for Polypeptide Charge Distributions Using Kohn-Sham One-electron Potential

doi:10.1007/s40242-025-5150-5

Abstract

Abstract: We introduce a quantum chemical topology (QCT) approach using the Kohn-Sham one-electron potential (KSpot) as a scalar function, revealing unique spatial features of atoms in molecules and the chemical bonds. The KSpot and its electron force lines demonstrate that an atom is a 3D basin governed by its nucleus as an attractor. Notably, KSpot atomic charges exhibit less basis set dependence, whose physical reliability is further confirmed through accurate reproduction of electrostatic potentials and dipole moments. To assess performance, we systematically compared KSpot QCT atomic charges with six established methods (QTAIM, Hirshfeld, Mülliken, NPA, CHELPG, and MK) across 20 amino acid dipeptides. KSpot charges have strong correlations with QTAIM and Hirshfeld ones, with correlation coefficients of 0.9207 and 0.9160, respectively. Furthermore, we successfully parameterized the atom bond electronegativity equalization method (ABEEM) using KSpot QCT charges, achieving a good linear agreement between them. These results establish KSpot QCT as a robust tool for molecular structure analysis, electrostatic interaction studies, and force field development.

Key words: Kohn-Sham one-electron potential (KSpot), Quantum chemical topology (QCT), Atomic charge, Polypeptide, Atom-bond electronegativity equalization method

GUO Xin, CONG Yunhong, ZHAO Jian, ZHAO Dongxia, YANG Zhongzhi. Developing Quantum Chemical Topology for Polypeptide Charge Distributions Using Kohn-Sham One-electron Potential[J]. Chemical Research in Chinese Universities, 2025, 41(5): 1121-1132.

References

[1] Belokoneva E., Smirnitskaya Y. Y., Tsirel'Son V. G., Russian Journal of Inorganic Chemistry, 1993, 38, 1252.
[2] Kapphahn M., Tsirelson V. G., Ozerov R. P., Doklady Akademii Nauk SSSR, 1989, 303, 1025.
[3] Cho M., Sylvetsky N., Eshafi S., Santra G., Efremenko I., Martin J. M. L., ChemPhysChem, 2020, 21, 688.
[4] Verstraelen T., Vandenbrande S., Heidar-Zadeh F., Vanduyfhuys L., Van Speybroeck V., Waroquier M., Ayers P. W., Journal of Chemical Theory and Computation, 2016, 12, 3894.
[5] Wang B., Truhlar D. G., Journal of Chemical Theory and Computation, 2014, 10, 4480.
[6] Verstraelen T., Ayers P. W., Van Speybroeck V., Waroquier M., Journal of Chemical Theory and Computation, 2013, 9, 2221.
[7] Manz T. A., Sholl D. S., Journal of Chemical Theory and Computation, 2010, 6, 2455.
[8] Verstraelen T., Bultinck P., Van Speybroeck V., Ayers P. W., Van Neck D., Waroquier M., Journal of Chemical Theory and Computation, 2011, 7, 1750.
[9] Wang B., Truhlar D. G., Journal of Chemical Theory and Computation, 2012, 8, 1989.
[10] Mülliken R. S., The Journal of Chemical Physics, 1962, 36, 3428.
[11] Mülliken R. S., The Journal of Chemical Physics, 1955, 23, 2343.
[12] Mülliken R. S., The Journal of Chemical Physics, 1955, 23, 2338.
[13] Glendening E. D., Landis C. R., Weinhold F., WIREs Computational Molecular Science, 2011, 2, 1.
[14] Reed A. E., Weinstock R. B., Weinhold F., The Journal of Chemical Physics, 1985, 83, 735.
[15] Hirshfeld F. L., Theoretica Chimica Acta, 1977, 44, 129.
[16] Lu T., Chen F. W., Journal of Theoretical and Computational Chemistry, 2012, 11, 163.
[17] Singh U. C., Kollman P. A., Journal of Computational Chemistry, 1990, 11, 361.
[18] Breneman C. M., Wiberg K. B., Journal of Computational Chemistry, 1990, 11, 361.
[19] Bayly C. I., Cieplak P., Cornell W. D., Kollman P. A., The Journal of Physical Chemistry, 1993, 97, 10269.
[20] Gou Q. L., Su Q., Wang J. K., Zhang H. X., Sun H. Y., Zhang X. J., Jiang L. L., Fang M. J., Kang Y., Liu H. X., Hou T. J., Hsieh C. Y., Journal of Chemical Information and Modeling, 2025, https://doi.org/10.1021/acs.jcim.5c00602.
[21] Storer J. W., Geiesen D. J., Cramer C. J., Truhlar D. J., Journal of Computer-Aided Molecular Design, 1995, 9, 87.
[22] Li J. B., Zhu T. H., Cramer C. J., Truhla D. G., The Journal of Physical Chemistry A, 1998, 102, 1820.
[23] Winget P., Thompson J. D., Xidos J. D., Cramer C. J., Truhlar D. G., The Journal of Physical Chemistry A, 2002, 106, 10707.
[24] Cramer C. J., Essentials of Computational Chemistry, John Wiley & Sons, England, 2004.
[25] Olson R. M., Marenich A. V., Cramer C. J., Truhlar D. G., Journal of Chemical Theory and Computation, 2007, 3, 2046.
[26] Marenich A. V., Jerome S. V., Cramer C. J., Truhlar D. G., Journal of Chemical Theory and Computation, 2012, 8, 527.
[27] Cioslowski J., Journal of The American Chemical Society, 1989, 111, 8336.
[28] Cioslowski J., Physical Review Letters, 1989, 62, 1469.
[29] Parr R. G., Yang W., Density Functional Theory of Atoms and Molecules, Oxford University Press, New York, 1989.
[30] Mortier W. J., Van Genechten K., Gasteiger J., Journal of the American Chemical Society, 1985, 16, 829.
[31] Mortier W. J., Ghosh S. K., Shankar S., Journal of the American Chemical Society, 1986, 108, 4315.
[32] Nomura K., Small P. E., Kalia R. K., Nakano A., Vashishta P., Computer Physics Communications, 2015, 192, 91.
[33] York D. M., Yang W. T., The Journal of Chemical Physics, 1996, 104, 159.
[34] Gasteiger J., Marsili M., Tetrahedron Letter, 1978, 19, 3181.
[35] Gasteiger J., Marsili M., Tetrahedron Letter, 1980, 36, 3219.
[36] No K. T., Grant J. A., Scheraga H. A., Journal of Physical Chemistry, 1990, 94, 4732.
[37] Park J. M., Tai No K., Jhon M. S., Scheraga H. A., Journal of Computational Chemistry, 1993, 14, 1482.
[38] Mullay J., Journal of The American Chemical Society, 1986, 108, 1770.
[39] Abraham R. J., Hudson B., Journal of Computational Chemistry, 1982, 3, 407.
[40] Abraham R. J., Paul E. S., Journal of Computational Chemistry, 1988, 9, 288.
[41] Yang Z. Z., Wang C. S., The Journal of Physical Chemistry A, 1997, 101, 6315.
[42] Cong Y., Yang Z. Z., Chemical Physics Letters, 2000, 316, 324.
[43] Yang Z. Z., Wu Y., Zhao D. X., The Journal of Chemical Physics, 2004, 120, 2541.
[44] Yang Z. Z., Cui B. Q., Journal of Chemical Theory and Computation, 2007, 3, 1561.
[45] Zhao D. X., Liu C., Wang F. F., Yu C. Y., Gong L. D., Liu S. B., Yang Z. Z., Journal of Chemical Theory and Computation, 2010, 6, 795.
[46] Liu C., Li Y., Han B. Y., Gong L. D., Lu L. N., Yang Z. Z., Zhao D. X., Journal of Chemical Theory and Computation, 2017, 13, 2098.
[47] Froitzheim T., Müller M., Hansen A., Grimme S., The Journal of Chemical Physics, 2025, 162, 214109.
[48] Bader R. F. W., MacDougall P. J., Lau C. D. H., Journal of The American Chemical Society, 1984, 106, 1594.
[49] Bader R. F. W., Chemical Review, 1991, 91, 893.
[50] Bader R. F. W., Accounts of Chemical Research, 1985, 18, 9.
[51] Zhao D. X., Zhao J., Zhu Z. W., Zhang C., Yang Z. Z., International Journal of Quantum Chemistry, 2018, 118, 25610
[52] Zhao D. X., Zhao J., Yang Z. Z., The Journal of Physical Chemistry A, 2020, 124, 5023.
[53] Popelier P. L. A.; Eds.: Chauvin R., Lepetit C., Silvi B., Alikhani E., Applications of Topological Methods in Molecular Chemistry, Springer International Publishing AG Switzerland, Switzerland, 2016, 22, 23.
[54] Martıń Pendás A., Francisco E., Bueno A. G., Guevara Vela J. M., Costales A.; Eds.: Chauvin R., Lepetit C., Silvi B., Applications of Topological Methods in Molecular Chemistry; Springer International Publishing AG Switzerland, Switzerland, 2016, 22, 131.
[55] Hemeda A. A., Esteves R. J. A., McLeskey J. T., Gad-el-Hak M., Khraisheh M., Vahedi Tafreshi H., International Communications in Heat and Mass Transfer, 2018, 98, 304.
[56] Bhattacharjee N., Alonso-Cotchico L., Lucas M. F., Frontiers in Bioengineering and Biotechnology, 2023, 11, 15.
[57] Wang L. Y., Schauperl M., Mobley D. L., Bayly C., Gilson M. K., Journal of Chemical Theory and Computation, 2023, 20, 1293.
[58] Riniker S., Journal of Chemical Information and Modeling, 2018, 58, 565.
[59] Liang Q. J., Yang J., Journal of Chemical Theory and Computation, 2023, 21, 3360.
[60] Grigoriadis I., International Journal of Drug Safety and Discovery, 2019, 3, 1.
[61] Salo-Ahen O. M. H., Alanko I., Bhadane R., Bonvin A. M. J. J., Honorato R. V., Hossain S., Juffer A. H., Kabedev A., Lahtela-Kakkonen M., Larsen A. S., Lescrinier E., Marimuthu P., Mirza M. U., Mustafa G., Nunes-Alves A., Pantsar T., Saadabadi A., Singaravelu K., Vanmeert M., Processes, 2021, 9, 71.
[62] Jones R. O., Reviews of Modern Physics, 2015, 87, 897.
[63] Kohn W., Sham L. J., Physical Review, 1965, 140, A1133.
[64] Ospadov E., Tao J. M., Staroverov V. N., Perdew J. P., Proceedings of the National Academy of Sciences, 2018, 115, 11578.
[65] Wang C. S., Yang Z. Z., The Journal of Chemical Physics, 1999, 110, 6189.
[66] Liu C., Zhao J., Yang Z. Z., Zhao D. X., Journal of Chemical Theory and Computation, 2020, 16, 7618.
[67] Zhao C. L., Zhao D. X., Bei C. C., Meng X. N., Li S., Yang Z. Z., The Journal of Physical Chemistry B, 2019, 123, 4594.
[68] Zhao C. L., Zhao D. X., Jiang Q. Y., Zhang H. X., Li S. M., Yang Z. Z., The Journal of Physical Chemistry B, 2020, 124, 2450.
[69] Zhang J., Gong L. D., Yang Z. Z., Journal of Computational Biophysics and Chemistry, 2022, 21, 485.
[70] Zhang C., Zhao D. X., Feng Y., Wang J., Yang Z. Z., Physical Chemistry Chemical Physics, 2022, 24, 4232.
[71] Shi H., Gong L. D., Liu C., Lu L. N., Yang Z. Z., The Journal of Physical Chemistry A, 2020, 124, 5963.
[72] Huang H., Zhao D. X., Zhao J., Chen X., Liu C., Yang Z. Z., The Journal of Physical Chemistry B, 2024, 128, 3807.
[73] He L. L., Li Y., Zhao D. X., Yu L., Zhao C. L., Lu L. N., Liu C., Yang Z. Z., The Journal of Physical Chemistry C, 2019, 123, 5653.
[74] Lee C., Yang W., Parr R. G., Physical Review B, 1988, 37, 785.
[75] Becke A. D., The Journal of Chemical Physics, 1993, 98, 5648.
[76] Lang L., Frontera A., Perez A., Bauzá A., Journal of Chemical Information and Modeling, 2023, 63, 3018.
[77] Grimme S., The Journal of Chemical Physics, 2006, 124, 034108.
[78] Frisch M. J., Trucks G. W., Schlegel H. B., Scuseria G. E., Robb M. A., Cheeseman J. R., Scalmani G., Barone V., Mennucci B., Petersson G. A., Nakatsuji H., Caricato M., Li X., Hratchian H. P., Izmaylov A. F., Bloino J., Zheng G., Sonnenberg J. L., Hada M., Ehara M., Toyota K., Fukuda R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Vreven T., Montgomery J. A. J., Peralta J. E., Ogliaro F., Bearpark M., Heyd J. J., Brothers E., Kudin K. N., Staroverov V. N., Kobayashi R., Normand J., Raghavachari K., Rendell A., Burant J. C., Iyengar S. S., Tomasi J., Cossi M., Rega N., Millam J. M., Klene M., Knox J. E., Cross J. B., Balkken V., Adamo C., Jaramillo J., Gomperts R., Stratmann R. E., Yazyev O., Austin A. J., Cammi R., Pomelli C., Ochterski J. W., Martin R. L., Morokuma K., Zakrzewski V. G., Voth G. A., Salvador P., Dannenberg J. J., Dapprich S., Daniels A. D., Farkas F., Foresman J. B., Ortiz J. V., Cioslowski J., Fox D. J., Gaussian 09 (Revision D. 01), Gaussian, Inc., Wallingford CT, 2009.
[79] Lu T., Chen F. W., Journal of Computational Chemistry, 2012, 33, 580.
[80] Lu T., The Journal of Chemical Physics, 2024, 161, 082503.
[81] Zhang C., Conformation and Coupling Constant of Oligopeptide in Vacuum and Aqueous Solution with Developing Abeem Polarizable Force Field, Liaoning Normal University, Dalian, 2021, 290.
[82] MathWorks, Matlab (R2021b), The MathWorks, Inc., Natick, MA, 2012.