BACKGROUND: Partial atomic charges are a well-established concept, useful in understanding and modeling the chemical behavior of molecules, from simple compounds, to large biomolecular complexes with many reactive sites. RESULTS: This paper introduces AtomicChargeCalculator (ACC), a web-based application for the calculation and analysis of atomic charges which respond to changes in molecular conformation and chemical environment. ACC relies on an empirical method to rapidly compute atomic charges with accuracy comparable to quantum mechanical approaches. Due to its efficient implementation, ACC can handle any type of molecular system, regardless of size and chemical complexity, from drug-like molecules to biomacromolecular complexes with hundreds of thousands of atoms. ACC writes out atomic charges into common molecular structure files, and offers interactive facilities for statistical analysis and comparison of the results, in both tabular and graphical form. CONCLUSIONS: Due to high customizability and speed, easy streamlining and the unified platform for calculation and analysis, ACC caters to all fields of life sciences, from drug design to nanocarriers. ACC is freely available via the Internet at http://ncbr.muni.cz/ACC.

CEITEC Central European Institute of Technology Masaryk University Kamenice 5 625 00 Brno Czech Republic

Faculty of Informatics Masaryk University Botanická 68a 602 00 Brno Czech Republic

National Centre for Biomolecular Research Faculty of Science Masaryk University Kotlářská 2 611 37 Brno Czech Republic

Zobrazit více v PubMed

Giese B, Graber M, Cordes M (2008) Electron transfer in peptides and proteins. Curr Opin Chem Biol 12(6):755–759. doi:10.1016/j.cbpa.2008.08.026 PubMed

Grodick MA, Muren NB, Barton JK. DNA charge transport within the cell. Biochemistry. 2015;54(4):962–973. doi: 10.1021/bi501520w. PubMed DOI PMC

Li L, Wang L, Alexov E (2015) On the energy components governing molecular recognition in the framework of continuum approaches. Front Mol Biosci. doi:10.3389/fmolb.2015.00005 PubMed PMC

Zheng G, Xiao M, Lu XH. QSAR study on the Ah receptor-binding affinities of polyhalogenated dibenzo-p-dioxins using net atomic-charge descriptors and a radial basis neural network. Anal Bioanal Chem. 2005;383:810–816. doi: 10.1007/s00216-005-0085-7. PubMed DOI

Karelson M, Karelson G, Tämm T, Tulp I, Jänes J, Tämm K, Lomaka A, Deniss S, Dobchev D. QSAR study of pharmacological permeabilities. Arkivoc. 2009;2009(2):218–238. doi: 10.3998/ark.5550190.0010.222. DOI

Wood JS. An X-ray determination of the electron distribution in crystals of hexapyridine-N-oxide cobalt(II) perchlorate and the electronic structure of the Co2+ ion. Inorganica chimica acta. 1995;229(1–2):407–415. doi: 10.1016/0020-1693(94)04272-W. DOI

Belokoneva EL, Gubina YK, Forsyth JB, Brown PJ. The charge-density distribution, its multipole refinement and the antiferromagnetic structure of dioptase, DOI

Schrödinger E. An undulatory theory of the mechanics of atoms and molecules. Phys Rev. 1926;28(6):1049. doi: 10.1103/PhysRev.28.1049. DOI

Mulliken RS. Electronic structures of molecules XI. Electroaffinity, molecular orbitals and dipole moments. J Chem Phys. 1935;3(9):573–585. doi: 10.1063/1.1749731. DOI

Mulliken RS. Criteria for the construction of good self-consistent-field molecular orbital wave functions, and the significance of LCAO-MO population analysis. J Chem Phys. 1962;36(12):3428. doi: 10.1063/1.1732476. DOI

Löwdin P-O. On the non-orthogonality problem connected with the use of atomic wave functions in the theory of molecules and crystals. J Chem Phys. 1950;18(3):365–375. doi: 10.1063/1.1747632. DOI

Reed EA, Weinstock RB, Weinhold F. Natural population analysis. J Chem Phys. 1985;83(2):735–746. doi: 10.1063/1.449486. DOI

Bader RFW, Larouche A, Gatti C, Carroll MT, MacDougall PJ, Wiberg KB. Properties of atoms in molecules: dipole moments and transferability of properties. J Chem Phys. 1987;87(2):1142–1152. doi: 10.1063/1.453294. DOI

Hirshfeld FL. Bonded-atom fragments for describing molecular charge densities. Theoretica Chimica Acta. 1977;44(2):129–138. doi: 10.1007/BF00549096. DOI

Bultinck P, Van Alsenoy C, Ayers PW, Carbó-Dorca R. Critical analysis and extension of the Hirshfeld atoms in molecules. J Chem Phys. 2007 PubMed

Breneman CM, Wiberg KB. Determining atom-centered monopoles from molecular electrostatic potentials. The need for high sampling density in formamide conformational analysis. J Comput Chem. 1990;11(3):361–373. doi: 10.1002/jcc.540110311. DOI

Besler BH, Merz KM, Kollman PA. Atomic charges derived from semiempirical methods. J Comput Chem. 1990;11:431–439. doi: 10.1002/jcc.540110404. DOI

Kelly CP, Cramer CJ, Truhlar DG (2005) Accurate partial atomic charges for high-energy molecules using class IV charge models with the MIDI! basis set. Theor Chem Acc 113(3):133–151. doi: 10.1007/s00214-004-0624-x

Manz TA, Sholl DS. Chemically meaningful atomic charges that reproduce the electrostatic potential in periodic and nonperiodic materials. J Chem Theory Comput. 2010;6(8):2455–2468. doi: 10.1021/ct100125x. PubMed DOI

Abraham RJ, Griffiths L, Loftus P. Approaches to charge calculations in molecular mechanics. J Comput Chem. 1982;3(3):407–416. doi: 10.1002/jcc.540030316. DOI

Shulga DA, Oliferenko AA, Pisarev SA, Palyulin VA, Zefirov NS. Parameterization of empirical schemes of partial atomic charge calculation for reproducing the molecular electrostatic potential. Doklady Chem. 2008;419(1):57–61. doi: 10.1134/S001250080803004X. DOI

Mortier WJ, Ghosh SK, Shankar S. Electronegativity-equalization method for the calculation of atomic charges in molecules. J Am Chem Soc. 1986;108(15):4315–4320. doi: 10.1021/ja00275a013. DOI

Rappé AK, Goddard WA., III Charge equilibration for molecular dynamics simulations. J Phys Chem. 1991;95:3358–3363. doi: 10.1021/j100161a070. DOI

Nistor RA, Polihronov JG, Müser MH. A generalization of the charge equilibration method for nonmetallic materials. J Chem Phys. 2006 PubMed

Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity-a rapid access to atomic charges. doi:10.1016/0040-4020(80)80168-2

Cho K-H, Kang YK, No KT, Scheraga HA. A fast method for calculating geometry-dependent net atomic charges for polypeptides. J Phys Chem A. 2001;105(17):3624–3634. doi: 10.1021/jp0023213. DOI

Oliferenko AA, Pisarev SA, Palyulin VA, Zefirov NS (2006) Atomic charges via electronegativity equalization: generalizations and perspectives. doi:10.1016/S0065-3276(06)51004-4

Baekelandt B, Mortier W, Lievens J. Probing the reactivity of different sites within a molecule or solid by direct computation of molecular sensitivities via an extension of the electronegativity equalization. J Am Chem Soc. 1991;113(18):6730–6734. doi: 10.1021/ja00018a003. DOI

York DM, Yang W. A chemical potential equalization method for molecular simulations. J Chem Phys. 1996;104(1):159. doi: 10.1063/1.470886. DOI

Yang Z-Z, Wang C-S. Atom-bond electronegativity equalization method. 1. Calculation of the charge distribution in large molecules. J Phys Chem A. 1997;101(35):6315–6321. doi: 10.1021/jp9711048. DOI

Njo SL, Fan J, Van De Graaf B. Extending and simplifying the electronegativity equalization method. J Mol Catal A Chem. 1998;134:79–88. doi: 10.1016/S1381-1169(98)00024-7. DOI

Dias LG, Shimizu K, Farah JPS, Chaimovich H. A simple method for the fast calculation of charge redistribution of solutes in an implicit solvent model. Chem Phys. 2002;282(2):237–243. doi: 10.1016/S0301-0104(02)00717-6. DOI

Chaves J, Barroso JM, Bultinck P, Carbó-Dorca R. Toward an alternative hardness kernel matrix structure in the Electronegativity Equalization Method (EEM) J Chem Inform Model. 2006;46(4):1657–1665. doi: 10.1021/ci050505e. PubMed DOI

Ouyang Y, Ye F, Liang Y. A modified electronegativity equalization method for fast and accurate calculation of atomic charges in large biological molecules. Phys Chem Chem Phys PCCP. 2009;11(29):6082–6089. doi: 10.1039/b821696g. PubMed DOI

Verstraelen T, Van Speybroeck V, Waroquier M. The electronegativity equalization method and the split charge equilibration applied to organic systems: Parametrization, validation, and comparison. J Chem Phys. 2009 PubMed

Frisch M, Trucks G, Schlegel H, Scuseria G, Robb M, Cheeseman J, Scalmani G, Barone V, Mennucci B, Petersson G et al (2010) Gaussian 09 (revision a. 02), gaussian, inc., wallingford ct (USA). In: Naturforsch Z (ed) Vol. 10

Hutter J, Iannuzzi M, Schiffmann F, Vandevondele J. Cp2k: atomistic simulations of condensed matter systems. Wiley Interdiscip Rev Comput Mol Sci. 2014;4(1):15–25. doi: 10.1002/wcms.1159. DOI

Manz TA, Sholl DS. Improved atoms-in-molecule charge partitioning functional for simultaneously reproducing the electrostatic potential and chemical states in periodic and nonperiodic materials. J Chem Theory Comput. 2012;8(8):2844–2867. doi: 10.1021/ct3002199. PubMed DOI

Verstraelen T, Vandenbrande S, Chan M, Zadeh FH, González C, Limacher PA, Horton AM (2013). http://theochem.github.com/horton/

Keith TA (2013) Aimall (version 13.05. 06). TK Gristmill Software, Overland Park

Marenich AV, Jerome SV, Cramer CJ, Truhlar DG. Charge model 5: an extension of hirshfeld population analysis for the accurate description of molecular interactions in gaseous and condensed phases. J Chem Theory Comput. 2012;8(2):527–541. doi: 10.1021/ct200866d. PubMed DOI

Malde AK, Zuo L, Breeze M, Stroet M, Poger D, Nair PC, Oostenbrink C, Mark AE. An automated force field topology builder (ATB) and repository: Version 1.0. J Chem Theory Comput. 2011;7(12):4026–4037. doi: 10.1021/ct200196m. PubMed DOI

Medeiros DDJ, Cortopassi WA, Costa França TC, Pimentel AS. ITP adjuster 1.0: A new utility program to adjust charges in the topology files generated by the PRODRG server. J Chem. 2013

Wang J, Wang W, Kollman PA, Case DA. Automatic atom type and bond type perception in molecular mechanical calculations. J Mol Graph Modelling. 2006;25(2):247–260. doi: 10.1016/j.jmgm.2005.12.005. PubMed DOI

Vanquelef E, Simon S, Marquant G, Garcia E, Klimerak G, Delepine JC, Cieplak P, Dupradeau FY. R.E.D. Server: a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments. Nucl Acids Res. 2011 PubMed PMC

Mukherjee G, Patra N, Barua P, Jayaram B. A fast empirical GAFF compatible partial atomic charge assignment scheme for modeling interactions of small molecules with biomolecular targets. J Comput Chem. 2011;32(5):893–907. doi: 10.1002/jcc.21671. PubMed DOI

Vainio MJ, Johnson MS. Generating conformer ensembles using a multiobjective genetic algorithm. J Chem Inform Modeling. 2007;47(6):2462–2474. doi: 10.1021/ci6005646. PubMed DOI

Vařeková RS, Koča J. Software news and update optimized and parallelized implementation of the electronegativity equalization method and the atom-bond electronegativity equalization method. J Comput Chem. 2006;27(3):396–405. doi: 10.1002/jcc.20344. PubMed DOI

Dolinsky TJ, Nielsen JE, McCammon JA, Baker NA. PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations. Nucl Acids Res. 2004 PubMed PMC

O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open babel: an open chemical toolbox. J Cheminform. 2011 PubMed PMC

Cho AE, Guallar V, Berne BJ, Friesner R. Importance of accurate charges in molecular docking: Quantum Mechanical/Molecular Mechanical (QM/MM) approach. J Comput Chem. 2005;26(9):915–931. doi: 10.1002/jcc.20222. PubMed DOI PMC

Anisimov VM. Quantum-mechanical molecular dynamics of charge transfer. Kinetics Dynamics. 2010

Nielsen JE, Gunner MR, García-Moreno EB (2011) The pK a Cooperative: a collaborative effort to advance structure-based calculations of pK a values and electrostatic effects in proteins. doi:10.1002/prot.23194 PubMed PMC

Baker CM. Polarizable force fields for molecular dynamics simulations of biomolecules. Wiley Interdiscip Rev Comput Mol Sci. 2015;5(2):241–254. doi: 10.1002/wcms.1215. DOI

Heidler R, Janssens GOA, Mortier WJ, Schoonheydt RA. Charge sensitivity analysis of intrinsic basicity of Faujasite-type zeolites using the electronegativity equalization method (EEM) J Phys Chem. 1996;100(50):19728–19734. doi: 10.1021/jp9615619. DOI

Haldoupis E, Nair S, Sholl DS. Finding MOFs for highly selective CO2/N2 adsorption using materials screening based on efficient assignment of atomic point charges. J Am Chem Soc. 2012;134(9):4313–4323. doi: 10.1021/ja2108239. PubMed DOI

Bultinck P, Langenaeker W, Carbó-Dorca R, Tollenaere JP. Fast calculation of quantum chemical molecular descriptors from the Electronegativity Equalization Method. J Chem Inform Comp Sci. 2003;43:422–428. doi: 10.1021/ci0255883. PubMed DOI

Svobodová Vařeková R, Geidl S, Ionescu C-M, Skřehota O, Bouchal T, Sehnal D, Abagyan R, Koča J. Predicting p Ka values from EEM atomic charges. J Cheminform. 2013;5(1):18. doi: 10.1186/1758-2946-5-18. PubMed DOI PMC

Shimizu K, Chaimovich H, Farah JPS, Dias LG, Bostick DL. Calculation of the dipole moment for polypeptides using the generalized born-electronegativity equalization method: results in vacuum and continuum-dielectric solvent. J Phys Chem B. 2004;108(13):4171–4177. doi: 10.1021/jp037315w. DOI

Chen S, Yang Z. Molecular dynamics simulations of a DOI

Ionescu CM, Svobodová Vařeková R, Prehn JHM, Huber HJ, Koča J. Charge profile analysis reveals that activation of pro-apoptotic regulators bax and bak relies on charge transfer mediated allosteric regulation. PLoS Comput Biol. 2012 PubMed PMC

Chelli R, Procacci P, Righini R, Califano S. Electrical response in chemical potential equalization schemes. J Chem Phys. 1999;111(18):8569. doi: 10.1063/1.480198. DOI

Warren Lee G, Davis JE, Patel S. Origin and control of superlinear polarizability scaling in chemical potential equalization methods. J Chem Phy. 2008;128(14):144110. doi: 10.1063/1.2872603. PubMed DOI PMC

Verstraelen T, Pauwels E, De Proft F, Van Speybroeck V, Geerlings P, Waroquier M. Assessment of atomic charge models for gas-phase computations on polypeptides. J Chem Theory Comput. 2012;8(2):661–676. doi: 10.1021/ct200512e. PubMed DOI

van Duin ACT, Strachan A, Stewman S, Zhang Q, Xu X, Goddard WA. ReaxFF SiO reactive force field for silicon and silicon oxide systems. J Phys Chem A. 2003;107(19):3803–3811. doi: 10.1021/jp0276303. DOI

Puranen JS, Vainio MJ, Johnson MS. Accurate conformation-dependent molecular electrostatic potentials for high-throughput in silico drug discovery. J Comput Chem. 2009 PubMed

Bultinck P, Langenaeker W, Lahorte P, De Proft F, Geerlings P, Van Alsenoy C, Tollenaere JP. The electronegativity equalization method II: applicability of different atomic charge schemes. J Phys Chem A. 2002;106(34):7895–7901. doi: 10.1021/jp020547v. DOI

Bultinck P, Vanholme R, Popelier PLA, De Proft F, Geerlings P. High-speed calculation of AIM charges through the electronegativity equalization method. J Phys Chem A. 2004;108(46):10359–10366. doi: 10.1021/jp046928l. DOI

Varekova RS, Jirouskova Z, Vanek J, Suchomel S, Koca J. Electronegativity equalization method: parameterization and validation for large sets of organic, organohalogene and organometal molecule. Int J Mol Sci. 2007;8(7):572–582. doi: 10.3390/i8070572. DOI

Ionescu CM, Geidl S, Svobodová Vařeková R, Koča J. Rapid calculation of accurate atomic charges for proteins via the electronegativity equalization method. J Chem Inform Model. 2013;53(10):2548–2558. doi: 10.1021/ci400448n. PubMed DOI

Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF (2013) The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology 21(3):201–232. doi:10.1007/s10787-013-0172-x PubMed

Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S (2006) Paracetamol: new vistas of an old drug. CNS Drug Rev. 12(3–4):250–275. doi:10.1111/j.1527-3458.2006.00250.x PubMed PMC

Svobodová Vařeková R, Geidl S, Ionescu CM, Skřehota O, Kudera M, Sehnal D, Bouchal T, Abagyan R, Huber HJ, Koča J. Predicting pKa values of substituted phenols from atomic charges: comparison of different quantum mechanical methods and charge distribution schemes. J Chem Inform Modeling. 2011;51(8):1795–1806. doi: 10.1021/ci200133w. PubMed DOI

Ugur I, Marion A, Parant S, Jensen JH, Monard G. Rationalization of the pKa values of alcohols and thiols using atomic charge descriptors and its application to the prediction of aminoacid pKa’s. J Chem Inform Modeling. 2014 PubMed

Dastmalchi S, Rashidi M, Rassi M. Simultaneous determination of the pka and octanol/water partition coefficient (pm) of acetaminophen. J Sch Pharm Med Sci Univ Tehran. 1995;4:7–14.

NCI Open Database Compounds. National Cancer Institute. http://cactus.nci.nih.gov/. Accessed Aug 2015

Howard P, Meylan W. Physical/chemical property database (PHYSPROP) North Syracuse: Syracuse Research Corporation, Environmental Science Center; 1999.

Geidl S, Svobodová Vařeková R, Bendová V, Petrusek L, Ionescu CM, Jurka Z, Abagyan R, Koča J. How does the methodology of 3D structure preparation influence the quality of p K a prediction? J Chem Inform Modeling. 2015;55(6):1088–1097. doi: 10.1021/ci500758w. PubMed DOI PMC

Bellm L, Lehrer RI, Ganz T. Protegrins: new antibiotics of mammalian origin. Exp Opin Investig Drugs. 2000;9(8):1731–1742. doi: 10.1517/13543784.9.8.1731. PubMed DOI

Steinberg DA, Hurst MA, Fujii CA, Kung AHC, Ho JF, Cheng FC, Loury DJ, Fiddes JC. Protegrin-1: a broad-spectrum, rapidly microbicidal peptide with in vivo activity. Antimicrob Agents Chemotherap. 1997;41(8):1738–1742. PubMed PMC

Dong N, Zhu X, Chou S, Shan A, Li W, Jiang J. Antimicrobial potency and selectivity of simplified symmetric-end peptides. Biomaterials. 2014;35(27):8028–8039. doi: 10.1016/j.biomaterials.2014.06.005. PubMed DOI

Mohanram H, Bhattacharjya S. Cysteine deleted protegrin-1 (CDP-1): anti-bacterial activity, outer-membrane disruption and selectivity. Biochimica et Biophysica Acta (BBA) General Subjects. 2014;1840(10):3006–3016. doi: 10.1016/j.bbagen.2014.06.018. PubMed DOI

Ostberg N, Kaznessis Y. Protegrin structure-activity relationships: using homology models of synthetic sequences to determine structural characteristics important for activity. Peptides. 2005;26(2):197–206. doi: 10.1016/j.peptides.2004.09.020. PubMed DOI

Fahrner RL, Dieckmann T, Harwig SSL, Lehrer RI, Eisenberg D, Feigon J. Solution structure of protegrin-1, a broad-spectrum antimicrobial peptide from porcine leukocytes. Chem Biol. 1996;3(7):543–550. doi: 10.1016/S1074-5521(96)90145-3. PubMed DOI

Bolintineanu DS, Langham AA, Davis HT, Kaznessis YN (2007) Molecular dynamics simulations of three protegrin-type antimicrobial peptides: interplay between charges at the termini, PubMed PMC

Langham AA, Khandelia H, Schuster B, Waring AJ, Lehrer RI, Kaznessis YN. Correlation between simulated physicochemical properties and hemolycity of protegrin-like antimicrobial peptides: Predicting experimental toxicity. Peptides. 2008;29(7):1085–1093. doi: 10.1016/j.peptides.2008.03.018. PubMed DOI PMC

Lai JR, Huck BR, Weisblum B, Gellman SH. Design of non-cysteine-containing antimicrobial PubMed DOI

Bedford L, Paine S, Sheppard PW, Mayer RJ, Roelofs J (2010) Assembly, structure, and function of the 26S proteasome. doi:10.1016/j.tcb.2010.03.007 PubMed PMC

Gallastegui N, Groll M (2010) The 26S proteasome: assembly and function of a destructive machine. doi:10.1016/j.tibs.2010.05.005 PubMed

Unverdorben P, Beck F, Śledź P, Schweitzer A, Pfeifer G, Plitzko JM, Baumeister W, Förster F. Deep classification of a large cryo-EM dataset defines the conformational landscape of the 26S proteasome. Proc Natl Acad Sci USA. 2014;111(15):5544–5549. doi: 10.1073/pnas.1403409111. PubMed DOI PMC

O’Hara A, Howarth A, Varro A, Dimaline R. The role of proteasome beta subunits in gastrin-mediated transcription of plasminogen activator inhibitor-2 and regenerating protein1. PLoS One. 2013 PubMed PMC

Cron KR, Zhu K, Kushwaha DS, Hsieh G, Merzon D, Rameseder J, Chen CC, D’Andrea AD, Kozono D. Proteasome inhibitors block DNA repair and radiosensitize non-small cell lung cancer. PLoS One. 2013 PubMed PMC

αCharges: partial atomic charges for AlphaFold structures in high quality

Atomic Charge Calculator II: web-based tool for the calculation of partial atomic charges

The Eighth Central European Conference "Chemistry towards Biology": Snapshot

High-quality and universal empirical atomic charges for chemoinformatics applications