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Is the reductionist paradox an Achilles Heel of drug discovery?

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Notes

  1. This is a strategy that is somewhat akin to purchasing more lottery tickets in order to improve your chances of winning; unfortunately, winning the lottery is the same not as curing a disease.

  2. Side effects are in large measure due to off-target interactions that, among other things, are a reflection of the polypharmacology associated with most drugs and xenobiotics.

  3. Even the SDMT approaches are not enough to take account of the multitude of targets, many associated with the secondary, unwanted effects (vide supra).

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PUBLICATIONS — 1964 TO PRESENT: Activity Cliffs and Landscapes

  1. From Qualitative to Quantitative Analysis of Property Landscapes. Maggiora, G., Medina-Franco, J.L., Iqbal, J., Vogt, M. and Bajorath, J. J. Chem. Inf. Model. 60, 5873–5880 (2020).

  2. Conditional Probabilities of Activity Landscape Features for Individual Compounds. Vogt, M., Iyer, P., Maggiora, G.M., and Bajorath, J. J. Chem. Inf. Model. 53, 1602–1612 (2013).

  3. Activity Cliffs in PubChem Confirmatory Bioassays Taking Active Compounds into Account. Hu, Y., Maggiora, G.M., and Bajorath, J. J. Comput.-Aided Mol. Design 27, 115–124 (2013).

  4. Activity Landscapes, Information Theory, and Structure-Activity Relationships. Iyer, P., Stumpfe, D., Vogt, M., Bajorath, J. and Maggiora, G.M. Mol. Inf. 32, 421–430 (2013).

  5. Consensus Models of Activity Landscapes with Multiple Chemical, Conformer, and Property Representations. Yongye, A.B., Byler, K., Santos, R., Martinez-Mayorga, K., Maggiora, G.M., and Medina-Franco, J.L. J. Chem. Inf. Model. 51, 1259–1270 (2011).

  6. On Outliers and Activity Cliffs-Why QSAR Often Disappoints. Maggiora, G.M. J. Chem. Inf. Model. 46, 1535 (2006).

Chemical Informatics and Modeling

  1. The Impact of Chemoinformatics on Drug Discovery in the Pharmaceutical Industry. Martínez-Mayorga, K., Madariaga-Mazon, A., Medina-Franco, J.L., and Maggiora, G.M. Expert Opin. Drug Disc. (2020), (doi: https://doi.org/10.1080/17460441.2020.1696307).

  2. A Simple Mathematical Approach to the Analysis of Polypharmacology and Polyspecificity Data.

  3. Maggiora, G.M. and Gokhale, V. F1000Research, 6 (2017) (Chem Inf Sci):788 (doi: https://doi.org/10.12688/f1000research.11517.1). (2017).

  4. Non-Specificity of Drug-Target Interactions – Consequences for Drug Discovery. Maggiora, G.M. and Gokhale, V. In Frontiers in Molecular Design and Chemical Information Science, J. Bajorath, and V. Shanmugasundaram, V, Eds. American Chemical Society Press, Chapter 7 (2016).

  5. Softening the Rule of Five – Where to Draw the Line? Petit, J., Meurice, N., Kaiser, C., and Maggiora, G.M. Bioorg. Med. Chem. 20, 5343- 5351(2012).

  6. Large Compound Databases for Structure-Activity Relationships Studies in Drug Discovery. Scior, J. T., Bernard, P., Medina-Franco, J. L., and Maggiora, G. M. Mini-Rev. Med. Chem. 7, 851–860 (2007).

  7. A Similarity-Based Data-Fusion Approach to the Visual Characterization and Comparison of Compound Databases. Medina-Franco, J. L., Maggiora, G. M., Giulianotti, M. A., Pinilla, C., and Houghten, R. A. Chem. Biol. Drug. Des. 70, 393–412 (2007).

  8. Hierarchical Strategy for Identifying Active Chemotype Classes in Compound Databases. Medina-Franco, J.L., Petit, J., Maggiora, G.M. Chem. Biol. & Drug Design 67, 395–408 (2006).

  9. Evaluating High-Throughput Screening Calculations. Lang, P.T., Kuntz, I.D., Maggiora, G.M., and Bajorath, J. J. Biomolec. Screen. 10, 649–652 (2005).

  10. Hit-Directed Nearest-Neighbor Searching. Shanmugasundaram, V., Maggiora, G.M., and Lajiness, M.S. J. Med. Chem. 48, 240–248 (2005).

  11. A Practical Strategy for Directed Compound Acquisition. Maggiora, G.M., Shanmugasundaram, V., Lajiness, M.S., Doman, T.N., and Schulz, M.W. In Cheminformatics in Drug Discovery , T. Oprea, Ed., WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim, pp. 317–332 (2004).

  12. Data Shaving: A Focused Screening Approach. Schreyer, S.K., Parker, C.N., and Maggiora, G.M. J. Chem. Inf. Comput. Sci. 44, 470–479 (2004).

  13. Computer-Aided Decision Making in Pharmaceutical Research. Maggiora, G.M. In Proceedings of 2002 Beilstein Workshop on Molecular Informatics: Confronting Complexity, M. Hicks & C. Kettner (Eds.), held in Bolzano, Italy, May 13–16, 2002, pp. 149–166 (2003).

  14. Field-Based Similarity Forcing in Energy Minimization and Molecular Matching. Blinn, J.R., Rohrer, D.C., and Maggiora, G.M. Proceedings of the Pacific Symposium on Biocomputing ’99, R.B. Altman, A.K. Dunker, L. Hunter, and T.E. Klein, Eds., World Scientific, Singapore, pp. 415–425 (1998).

  15. A Molecular Field-Based Similarity Study of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors. Mestres, J., Rohrer, D.C., Maggiora, G.M. J. Comput.-Aided Molec. Design 13, 79–93 (1999).

  16. A Molecular Field-Based Similarity Approach to Pharmacophore Pattern Recognition. Mestres, J., Rohrer, D.C., and Maggiora, G.M. J. Molec. Graphics 15, 114–121 (1997).

  17. Application of the Shape Group Method to Conformational Processes: Shape and Conjugation Changes in the Conformers of 2-Phenyl-Pyrimidine. Walker, P.D., Mezey, P.G., Maggiora, G.M., Johnson, M.A., and Petke, J.D. J. Comput. Chem. 99, 4947–4954 (1995).

  18. Shape Group Analysis of Molecular Similarity: Shape Similarity of Six-Membered Aromatic Ring Systems. Walker, P.D., Maggiora, G.M., Johnson, M.A., Petke, J.D., and Mezey, P.G. J. Chem. Inf. Comput. Sci. 35, 568–578 (1995).

  19. Solvation Thermodynamics of Polar Molecules in Aqueous Solution by the XRISM Method. Lee, P. H. and Maggiora, G. M. J. Phys. Chem. 97, 10175–10185 (1993).

  20. Looking for Buried Treasures: The Search for New Drug Leads in Large Chemical Data Bases. Maggiora, G. M., Johnson, M. A., Lajiness, M. S., Miller, A. B. and Hagadone, T. R. Mathl. Comput. Modeling 11, 626–629 (1988).

  21. A Characterization of Molecular Similarity Methods for Property Prediction. Johnson, M. A., Basak, S. and Maggiora, G. M. Mathl. Comput. Modeling , 11, 630–634 (1988).

Commentaries and Reviews

  1. Is imatinib a prototypical example of targeted drug therapy? Maggiora, G.M., Future Med. Chem. 8, 1907–1911 (2016).

  2. Is There a Future for Computational Chemistry in Drug Research? Maggiora, G.M., J. Comput.-Aided Mol. Design 26, 87–90 (2012).

  3. The Reductionist Paradox: Are the Laws of Chemistry and Physics Sufficient for the Discovery of New Drugs? Maggiora, G.M., J. Comput.-Aided Mol. Design 25, 699–708.

  4. Emergence of the Concept of Molecular Diversity at Pharmacia. Lajiness, M.S., Johnson, M.A., and Maggiora, G.M. Invited submission for a Special Article on “Diverse Viewpoints on Computational Aspects of Molecular Diversity, Y. Martin (Ed.), J. Combinat. Chem. 3, 231–250 (2000).

  5. FORWARD to the book Molecular Structure Description: The Electrotopological State, L.B. Kier & L.H. Hall, Academic Press, San Diego, pp. xiii-xv, forward by Maggiora, G.M. (1999).

  6. Computer-Assisted Drug Discovery: Present and Future. Gund, P., Maggiora, G. M., and Snyder, J. P. Guidebook on Molecular Modeling in Drug Design, N. C. Cohen, Ed., Academic Press, London, pp. 219–233 (1996).

  7. Three Dimensional Chemical Structure Handling. Maggiora, G. M. Book review: by P. Willett, John Wiley & Sons, New York. Comput. Chem. 16, 270 (1992).

  8. Symposium Overview, Minnesota Conference on Supercomputing in Biology: Proteins, Nucleic Acids, and Water. Wilcox, G. L., Quiocho, F. A., Levinthal, C., Harvey, S. C., Maggiora, G. M. and McCammon, A. J. J. Comp. Aided Mol. Design 1, 271–281 (1988).

  9. Book review of “Quantum Chemistry,” by John P. Lowe Maggiora, G.M. Amer. Sci . 68, 205–206 (1980).

Electronic Structure Studies — Ground and Excited States

  1. Ab Initio Configuration Interaction and Random Phase Approximation Calculations of the Excited Singlet and Triplet States of Uracil and Cytosine. Petke, J. D., Maggiora, G. M., and Christofferson, R. E. J. Phys. Chem. 96, 6992–7001 (1992).

  2. Ab Initio Configuration Interaction and Random Phase Approximation Calculations of the Excited Singlet and Triplet States of Adenine and Guanine. Petke, J. D., Maggiora, G. M. and Christoffersen, R. E. J. Am. Chem. Soc. 112, 5452–5460 (1990).

  3. Quantum Mechanical SCF/CI Studies as Probes of Macromolecular Structure: Methodological Aspects of Spectral Comparisons. Petke, J. D., Maggiora, G. M. and Christoffersen, R. E. In Computer-Assisted Modeling of Receptor-Ligand Interactions: Theoretical Aspects and Applications to Drug Design , R. Rein, Ed., Alan R. Liss, Inc., New York, pp. 373–383 (1989).

  4. Investigation of Ab Initio HF-SCF-CI Methods for Calculating Rotatory Strengths in (R)-3 Methylcyclobutene. Chabalowsky, C., Maggiora, G.M., and Christoffersen, R.E. J. Am. Chem. Soc . 107, 1632–1640 (1984).

  5. Quantum Mechanical Characterization of the Low-Lying Singlet and Triplet States of Anthraquinone, Quinizarin, and 1,4-Dihydroxy Anthraquinone. Petke, J.D., Butler, P., and Maggiora, G.M. Int. J. Quantum Chem. 27, 71–87 (1984).

  6. Ab Initio Calculations on Large Molecules Using Molecular Fraagments. SCF MO CI Studies of Low-Lying Singlet and Triplet States of Pyrazine. Petke, J.D., Christoffersen, R.E., Maggiora, G.M., and Shipman, L.L. Int. J. Quantum Chem.: Quantum Biol. Symp. No. 4 , pp. 343-355 (1976).

Information Theory

  1. Application of Shannon-Like Diversity Measures to Cell-Based Chemistry Spaces. Shanmugasundaram, V. and Maggiora, G.M. J. Math. Chem. 49, 342–355 (2011).

  2. An Information-Theoretic Characterization of Partitioned Property Spaces. Maggiora, G.M. and Shanmugasundaram, V. J. Math. Chem. 38, 1–2 (2004).

Methods Development and Applications

  1. Dipole Sums and Intermolecular Interaction Coefficients Derived from Refractive Index Data. Yoffe, J. A., Maggiora, G. M., and Amos, A. T. Theoret. Chim. Acta 69, 461–473 (1986).

  2. Intermolecular Interaction Energies from Minimal-Basis SCF Calculations. Interactions Pertinent to Formaldehyde Hydration. Maggiora, G.M. and Williams, I.H. J. Mol. Struct. (THEOCHEM), 88, 23–35 (1982).

  3. Development of a Flexible Intra- and Intermolecular Empirical Potential Function for Large Molecular Systems. Oie, T., Maggiora, G.M., Christoffersen, R.E., and Duchamp, D.J. Int. J. Quantum Chem.: Quantum Biol. Symp. No. 8 , pp. 1-49 (1981).

  4. Development of Theoretical Methodology for Large Molecules. Maggiora, G.M., Christoffersen, R.E., Yoffe, J.A., and Petke, J.D. Ann. New York Acad. Sci. 367, 1–16 (1981).

  5. Some Rules for S(-2k) Dipole Sums. Yoffe, J.A., Maggiora, G.M., and Amos, A.T. Theoret. Chim. Acta 58, 137–144 (1981).

  6. The London Approximation and the Calculation of Dispersion Interaction as a Sum of Atom-Atom Terms. Yoffe, J.A. and Maggiora, G.M. Theoret. Chim. Acta 56,191–198 (1980).

  7. Ab Initio Calculations on Large Molecules Using Molecular Fragments. Generalization and Characteristics of Floating Spherical Gaussian Basis Sets. Maggiora, G.M. and Christoffersen, R.E. J. Am. Chem. Soc ., 98, 8325–8332 (1976).

  8. Ab Initio Calculations on Large Molecules Using Molecular Fragments. Unrestricted Hartree-Fock Calculations of the Low-Lying States of Formaldehyde and its Radical Ions. Davis, T.D., Maggiora, G.M., and Christoffersen, R.E. J. Am. Chem. Soc ., 96, 7878–7887 (1974).

  9. Ab Initio Calculations on Large Molecules Using Molecular Fragments. Evaluation and Extension of Initial Procedures. Christoffersen, R.E., Spangler, D., Hall, G.G., and Maggiora, G.M. J. Am. Chem. Soc . 95, 8526–8536 (1973).

  10. Ab Initio Calculations on Large Molecules Using Molecular Fragments. Initial Studies on Open-Shell Systems. Davis, T.D., Christoffersen, R.E., and Maggiora, G.M. Chem. Phys. Letts . 21, 576–580 (1973).

  11. Transferability of Molecular Fragments to Large Molecules. Christoffersen, R.E., Shipman, L.L., and Maggiora, G.M. Int. J. Quantum Chem. 58, 143–149 (1971).

  12. Ab Initio Calculations on Large Molecules Using Molecular Fragments. First-Order Electronic Properties for Hydrocarbons. Maggiora, G.M., Genson, D.E., Christoffersen, R.E., and Cheney, B.V. Theoret. Chim. Acta 22, 337–352 (1971).

  13. Ab Initio Calculations on Large Molecules Using Molecular Fragments. Hydrocarbon Characterizations. Christoffersen, R.E., Genson, D.E., and Maggiora, G.M. J. Chem. Phys . 54, 239–252 (1971).

  14. Ab Initio Calculations on Large Molecules Using Molecular Fragments. Preliminary Investigations. Christoffersen, R.E. and Maggiora, G.M. Chem. Phys. Letts ., 3, 419–423 (1969).

Miscellaneous

  1. Prospective feasibility trial for genomics-informed treatment in recurrent and progressive glioblastoma. Byron, S.A., Tran, N.L., Halperin, R.F., Philips, J.J., Kuhn, J.G., de Groot, J.F., H. Colman, H., Ligon, K. L., Wen, P.Y., Cloughesy, T.F., Mellinghoff, I.K., Butowski, N.A., Taylor2, J.W., Clarke, J.L., Chang, S.M., Berger, M.S., Molinaro, A.M., Maggiora, G.M., Peng, S., Nasser, S., Liang, W.S. Trent, J.M., Berens, M.E., Carpten, J.D. Craig, D.W., Prados, M.D. Clin. Cancer Res. DOI: https://doi.org/10.1158/1078-0432.CCR-17-0963 (2017).

  2. A Cell-Based Fascin Bioassay Identifies Compounds with Potential Anti-Metastasis or Cognitive-Enhancing Functions. Kraft, R., Kahn, A., Medina-Franco, J., Orlowski, M., Baynes, C., Vallejo, F., Barnard, K., Maggiora, G.M., and Restifo, L.L. Dis. Model. Mech. 6, 217–235 (2013).

  3. Mixture-based Synthetic Combinatorial Libraries: Direct in vivo Testing, Scaffold Ranking, and Enhanced Deconvolution Using Computational Approaches. Houghten, R. A., Pinilla, C., Appel, J. R., Giulianotti, M. A., Nefzi, A., Ostresh, J. M., Dooley, C.T., Maggiora, G. M., Medina Franco, J. L., Brunner, D., and Schneider, J. J. Comb. Chem. 10, 3–19 (2008).

  4. Synthesis of Platinum(II) Chiral Tetraamine Coordination Complexes. Nefzi, A., Hoesl, C.E., Kauffman, G.B., Maggiora, G.M., and Houghton, R.A. J. Combin. Chem. 8, 780–783 (2006).

  5. An Assessment of the Consistency of Medicinal Chemists in Reviewing Compound Lists. Lajiness, M.S., Maggiora, G.M., and Shanmugasundaram, V. J. Med. Chem. 47, 4891–4896 (2004).

Molecular Similarity

  1. An Introduction to Molecular Similarity and Chemical Spaces. Maggiora, G.M. In Food Science Informatics , K. Martinez-Mayorga & J.L. Medina-Franco, Eds. John Wiley & Sons, New York, pp. 1–81 (2014).

  2. Molecular Similarity Analysis. Medina-Franco, J.L. and Maggiora, G.M. In Chemoinformatics for Drug Discovery, J. Bajorath, Ed., John Wiley & Sons, New York, pp. 343–399 (2014).

  3. Molecular Similarity in Medicinal Chemistry (Mini-Perspective). Maggiora, G.M., Vogt, M., Stumpfe, D., and Bajorath, J. J. Med. Chem. 57, 3186–3204 (2014).

  4. Molecular Similarity Measures. Maggiora, G.M. and Shanmugasundaram, V. In Chemoinformatics and Computational Chemical Biology , 2nd Ed., J. Bajorath, Ed., Humana Press, Springer Science + Business Press, New York, pp. 39–100 (2011).

  5. Molecular Basis Sets - A General Similarity-Based Approach for Representing Chemical Spaces. Raghavendra, A.S. and Maggiora, G.M. J. Chem. Inf. Model. 47, 1328–1340 (2007).

  6. Evaluating Molecular Similarity Using Reduced Representations of the Electron Density. Meurice, N., Maggiora, G.M., and Vercauteren, D.P. J. Mol. Model. 11, 237–247 (2005)

  7. Putting Molecular Similarity into Context: Asymmetric Indices for Field-Based Similarity Measures. Mestres, J. and Maggiora, G.M. J. Math. Chem. 39, 107–118 (2005).

  8. A General Analysis of Field-Based Molecular Similarity Indices. Maggiora, G.M., Petke, J.D., and Mestres, J. J. Math. Chem. 31, 251–270 (2002).

  9. Molecular Similarity Measures. Maggiora, G.M. and Shanmugasundaram, V. In Chemoinformatics: Concepts, Methods, and Tools for Drug Discovery , 1st Ed., J. Bajorath, Ed., Humana Press, Totowa, NJ, pp. 1–50 (2004).

  10. A General Analysis of Field-Based Molecular Similarity Indices. Maggiora, G.M., Petke, J.D., and Mestres, J. J. Math. Chem. 31, 251–270 (2002).

  11. A General Analysis of Field-Based Molecular Similarity Indices. Mestres, J., Rohrer, D.C., and Maggiora, G.M. MIMIC: A Molecular Field Matching Program. Exploiting the Applicability of Molecular Similarity Approaches. J. Comput. Chem. 18, 934–954 (1997).

  12. Four Association Coefficients for Relating Molecular Similarity Measures. Cheng, C., Maggiora, G. M., Lajiness, M.S., and Johnson, M.A. J. Chem. Inf. Comput. Sci. 36, 909–915 (1996).

  13. Molecular Similarity Analysis: Applications in Drug Discovery. Johnson, M. A., Maggiora, G. M., Lajiness, M.S., Moon, J.B., Petke, J.D., and Rohrer, D.C. Chemometric Methods in Molecular Design , H.V. Waterbeemd, Ed., Verlag-Chemie, Weinheim, pp. 89–110 (1994).

  14. Introduction to Similarity in Chemistry. Maggiora, G. M. and Johnson, M. A. In Concepts and Applications of Molecular Similarity , M.A. Johnson and G.M. Maggiora, Eds., John Wiley & Sons, New York, Chapter 1 (1990).

  15. Concepts and Applications of Molecular Similarity (Book). Johnson, M. A. and Maggiora, G. M., Eds. John Wiley & Sons, New York, pp. 393 (1990).

  16. Molecular Similarity: A Basis for Designing Drug Screening Programs. Johnson, M. A., Lajiness, M. S. and Maggiora, G. M. In QSAR: Quantitative Structure-Activity Relationships in Drug Design, J.L. Fauchère, Ed., Alan Liss, Inc., New York, pp. 173–176 (1989).

  17. Implementing Drug Screening Programs Using Molecular Similarity Methods. Lajiness, M. S., Johnson, M. A. and Maggiora, G. M. In QSAR: Quantitative Structure-Activity Relationships in Drug Design , J.L. Fauchère, Ed., Alan Liss, Inc., New York, pp. 167–171 (1989).

Networks

  1. Comparison of bioactive chemical space networks generated using substructure- and fingerprint-based measures of molecular similarity. Zhang, B., Vogt, M., Maggiora, G.M., and Bajorath, J. J. Comput.-Aided Mol. Design 29, 595–608 (2015).

  2. Design and characterization of chemical space networks for different compound data sets. Zwierzyna, M., Vogt, M., Maggiora, G.M., and Bajorath, J. J. Comput.-Aided Mol. Design 29, 113–125 (2015).

  3. Chemical space networks – a powerful new paradigm for the description of chemical spaces. Maggiora, G.M. and Bajorath, J. J. Comput.-Aided Mol. Design 28, 795–802 (2014).

Neural Networks

  1. Artificial Neural Networks: A New Computational Paradigm with Applications in Chemistry. Maggiora, G. M. and Elrod, D. W. Proceedings, 16th International On-Line Information Meeting , 8–10 December 1992, London, England, pp. 109–125 (1992).

  2. Computational Neural Networks as Model-Free Mapping Devices. Maggiora, G. M., Elrod, D. W., and Trenary, R. G., J. Chem. Inf. Comp. Sci ., 32, 732–741 (1992).

  3. Predicting Chemical Reactions with a Neural Network. Elrod, D. W., Maggiora, G. M., and Trenary, R. G., Predicting Chemical Reactions with a Neural Network. Computing in the 90's. The First Great Lakes Computer Science Conference Proceedings ," N. A. Sherwani, E. de Doncker, and J. A. Kapenga, Eds., Springer-Verlag, Berlin, pp. 392–398 (1991).

  4. Applications of Neural Networks in Chemistry. 2. A General Connectivity Representation for the Prediction of Regiochemistry. Elrod, D. W., Maggiora, G. M., and Trenary, R. G. Tetrahedron Comput. Meth. 3, 163–174 (1990).

  5. Applications of Neural Networks in Chemistry. 1. Prediction of Electrophilic Aromatic Substitution Reactions. Elrod, D. W., Maggiora, G. M. and Trenary, R. G. J. Chem. Inf. Comput. Sci . 30, 477–484 (1990).

Organic and Biochemistry — Structure and Mechanisms

  1. Reaction-Surface Topography for Hydride Transfer: ab initio MO Studies of Isoelectronic Systems CH3O + CH2O and CH3NH2 + CH2NH2. Williams, I. H., Miller, A. B., and Maggiora, G. M. J. Am. Chem. Soc . 112, 530–537 (1990).

  2. Linearity and the Unimportance of Tunneling in Hydride Transfer: Ab Initio MO Studies. Hutley, B. G., Mountain, A. E., Williams, I. H., Maggiora, G. M., and Schowen, R. L. Chem. Comm. 267–268 (1986).

  3. Theoretical Probes of Activated-Complex Structure and Properties: Substituent Effects in Carbonyl Addition. Williams, I. H., Spangler, D., Maggiora, G. M., and Schowen, R. L. J. Am. Chem. Soc. 107, 7717–7723 (1985).

  4. Determination and Characterization of a Transition-State for Water Formaldehyde Addition. Spangler, D., Williams, I.H., and Maggiora, G.M. J. Comput. Chem. 4, 524–541(1983).

  5. Theoretical Models for Solvation and Catalysis in Carbonyl Addition. Williams, I.H., Spangler, D., Femec, D.A., Maggiora, G.M., and Schowen, R.L. J. Am. Chem. Soc . 105 31–40 (1983).

  6. The Structure of Dinitrogen Pentoxide. Carpenter, J. and Maggiora, G.M. Chem. Phys. Letts . 87, 349–352 (1982).

  7. Use and Abuse of the Distinguished-Coordinate Method in Transition-State Structure Searches. Williams, I.H. and Maggiora, G.M. J. Mol. Struct. (THEOCHEM) 89, 365–378 (1982).

  8. Theoretical Models for Mechanism and Catalysis in Carbonyl Addition. Williams, I.H., Maggiora, G.M., and Schowen, R.L. J. Am. Chem. Soc. 102, 7831–7839 (1980).

  9. Theoretical Models of Transition-State Structure and Catalysis in Carbonyl Addition. Williams, I.H., Spangler, D., Femec, D.A., Maggiora, G.M., and Schowen, R.L. J. Am. Chem. Soc. 102, 6619–6621(1980).

  10. Quantum Mechanical Approaches to the Study of Enzymic Transition States. Maggiora, G.M. and Christoffersen, R.E. In Transition States in Biochemical Processes , R.L. Schowen and R.D. Gandour (Eds.), Plenum Press, New York, pp. 119–163 (1978).

  11. The Interplay of Theory and Experiment in Bio-Organic Chemistry: Three Case Histories. Maggiora, G.M. and Schowen, R.L. In A Survey of Bio-Organic Chemistry, E.E. Van Tamelin (Ed.), Academic Press, New York, pp. 173–229 (1977).

  12. Excited States of All-trans and 11-cis Retinal. All Valence-Electron SCF MO CI Calculations. Weimann, L.J., Maggiora, G.M., and Blatz, P.E. Int. J. Quantum Chem.: Quantum Biol. Symp. No. 2 , pp. 9-24 (1975).

  13. Proton Bridges in Enzyme Catalysis. Elrod, J.P., Gandour, R.D., Hogg, J.L., Kise, M., Maggiora, G.M., Schowen, R.L., and Venkatasuban, K.S. In Faraday Symposia of the Chemical Society , No. 10, pp. 145–153 (1975).

  14. Ab Initio Calculations on Large Molecules Using Molecular Fragments. Nitroxide Spin-Label Characterizations. Davis, T.D., Maggiora, G.M., and Christoffersen, R.E. J. Am. Chem. Soc . 97, 1347–1356 (1974).

  15. Coupling of Proton Motions in Catalytic Activated Complexes: Model Potential Surfaces for Hydrogen Bond Chains. Gandour, R., Maggiora, G.M., and Schowen, R.L.. J. Am. Chem. Soc . 96, 6967–6979 (1974).

  16. Theoretical Aspects of the Structural Chemistry of Biotin. II. Carboxylated Biotins. Maggiora, G.M. J. Theoret. Biol. 43, 51–64 (1973).

  17. Theoretical Aspects of the Structural Chemistry of Biotin. I. The Electronic Structure of Biotin and Protonated Biotins. Maggiora, G.M. J. Theoret. Biol . 41, 523–534 (1973).

  18. The Electronic Spectra of the Isomers of Reduced 1-Alkyl Nicotinamide. Maggiora, G.M., Johansen, H., and Ingraham, L.L. Arch. Biochem. Biophys ., 131, 352–358 (1969).

  19. A Theoretical Study of the Structure of Oxygen-Metallic Ion Complexes. Maggiora, G.M., Viale, R.O., and Ingraham, L.L. In Oxidases and Related Redox Systems , T.E. King, H.S. Mason, and M. Morrison (Eds.). John Wiley and Sons, Inc., Vol. 1, pp. 88–96 (1965).

  20. Molecular Orbital Evidence for Weiss’ Oxyhemoglobin Structure. Viale, R.O., Maggiora, G.M., and Ingraham, L.L. Nature 203, 183–184 (1964).

Photosynthetic and Related Systems

  1. Electronic Excited States of Biomolecular Systems: Ab Initio FSGO-Based Quantum Mechanical Methods with Applications to Photosynthetic and Related Systems. Maggiora, G. M., Petke, J. D., and Christoffersen, R. E. In Theoretical Models of Chemistry Bonding, Part 4 , Z. B. Maksic, Ed., Springer-Verlag, Berlin, pp. 66–102 (1990).

  2. Evaluation of Approximations in Molecular Exciton Theory. II. Applications to Oligomeric Systems of Interest in Photosynthesis. LaLonde, D. E., Petke, J. D., and Maggiora, G. J. Phys. Chem. 93, 608–614 (1989).

  3. Evaluation of Approximations in Molecular Exciton Theory I. Applications to Dimeric Systems of Interest in Photosynthesis. LaLonde, D. E., Petke, J. D., and Maggiora, G. M. J. Phys. Chem. 92, 4746–4752 (1988).

  4. Quantum Mechanical Studies of Charge-Transfer States in Porphyrin Heterodimers. Petke, J. D. and Maggiora, G. M. In Porphyrins: Excited States and Dynamics . M. Gouterman, P. M. Rentzepis, and K. D. Straub, Eds., American Chemical Society, Washington, D.C., pp. 20–50 (1986).

  5. Nature and Location of Excited Charge-Transfer States in Porphine-Magnesium-Porphine Dimers: Development of Preliminary Design Characteristics for Biomimetic Solar Energy Conversion Systems. Petke, J. D. and Maggiora, G. M. J. Chem. Phys. 84, 1640–1652 (1986).

  6. Experimental and Theoretical Studies of Schiff Base Chlorophylls. Maggiora, L.L., Petke, J.D., Gopal, D., Iwamoto, R. T., and Maggiora, G. M. Photochem. Photobiol . 42, 69–78 (1985).

  7. Theoretical Characterization of Proton-Induce Spectral Shifts in Schiff’s Base Porphyrins. Petke, J.D. and Maggiora, G.M. J. Am. Chem. Soc. 106, 3129–3133 (1984).

  8. Protonated Schiff’s Base Chlorophyll, A Model for P700? Maggiora, L.L. and Maggiora, G.M. Photochem. Photobiol . 39, 847–849 (1984).

  9. Nature and Location of Charge-Transfer States in the Magnesium Porphine-Porphine Dimer. Petke, J.D. and Maggiora, G.M. Chem. Phys. Letts. 105, 31–40 (1983).

  10. Structural Characterization of the Special-Pair Chlorophyll Dimer Model of P700. Oie, T., Maggiora, G.M., and Christoffersen, R.E. Int. J. Quantum Chem.: Quantum Biol. Symp. No. 9 , pp. 157-171 (1982).

  11. Stereoelectronic Properties of Photosynthetic and Related Systems. IX. Ab Initio Quantum Mechanical Characterization of the Electronic Structure and Spectra of the Chlorophyllide a and Pheophorbide a Anion Radicals. Petke, J.D., G.M. Maggiora, Shipman, L.L., and Christoffersen, R.E. Photochem. Photobiol . 36, 383–394 (1982).

  12. Stereoelectronic Properties of Photosynthetic and Related Systems. 10. Ab Initio Quantum Mechanical Characterization of the Excited States of Ethyl Chlorophyllide a Enol. Petke, J.D., Shipman, L.L., G.M. Maggiora, and Christoffersen, R.E. J. Am. Chem. Soc. 103, 4621–4623 (1981).

  13. Stereoelectronic Properties of Photosynthetic and Related Systems. IX. Ab Initio Quantum Mechanical Characterization of the Electronic Structure and Spectrum of the Bacteriochlorophyllide a Anion Radical. Petke, J.D., G.M. Maggiora, Shipman, L.L., and Christoffersen, R.E. Photochem. Photobiol. 33, 663–671 (1980).

  14. Stereoelectronic Properties of Photosynthetic and Related Systems. VIII. Ab Initio Quantum Mechanical Characterization of the Electronic Structure and Spectrum of the Bacteriopheophorbide a Anion Radical. Petke, J.D., G.M. Maggiora, Shipman, L.L., and Christoffersen, R.E. Photochem. Photobiol . 32, 661–667 (1980).

  15. Stereoelectronic Properties of Photosynthetic and Related Systems. VII. Ab Initio Quantum Mechanical Characterization of the Electronic Structure and Spectra of Chlorophyllide a and Bacteriochlorophyllide a Cation Radicals. Petke, J.D., G.M. Maggiora, Shipman, L.L., and Christoffersen, R.E. Photochem. Photobiol . 31, 243–257 (1980).

  16. Assessment of Reaction Center Special-Pair Chlorophyll Models. Maggiora, G.M. Int. J. Quantum Chem. 16, 331–352 (1979).

  17. Stereoelectronic Properties of Photosynthetic and Related Systems. VI. Ab Initio Configuration Interaction Calculations on the Ground and Lower Excited Singlet and Triplet States of Ethyl Bacteriochlorophyllide a and Ethyl Bacteriopheophorbide a . Petke, J.D., G.M. Maggiora, Shipman, L.L., and Christoffersen, R.E. Photochem. Photobiol . 32, 399–414 (1978).

  18. Stereoelectronic Properties of Photosynthetic and Related Systems. IV. Ab Initio Configuration Interaction Calculations on the Ground and Lower Excited Singlet and Triplet States of Ethyl Chlorophyllide a and Ethyl Pheophorbide a . Petke, J.D., G.M. Maggiora, Shipman, L.L., and Christoffersen, R.E. Photochem. Photobiol . 30, 203–223 (1978).

  19. Stereoelectronic Properties of Photosynthetic and Related Systems. Ab Initio Configuration Interaction Calculations on the Ground and Lower Excited Singlet and Triplet States of Magnesium Chlorin, and Chlorin. Petke, J.D., G.M. Maggiora, Shipman, L.L., and Christoffersen, R.E. J. Spectrosc. 73, 311–331 (1978).

  20. Stereoelectronic Properties of Photosynthetic and Related Systems. Ab Initio Configuration Interaction Calculations on the Ground and Lower Excited Singlet and Triplet States of Magnesium Porphine, and Porphine. Petke, J.D., G.M. Maggiora, Shipman, L.L., and Christoffersen, R.E. J. Spectrosc . 71, 63–84 (1978).

  21. Stereoelectronic Properties of Photosynthetic and Related Systems. Ground State Characterization of Magnesium Porphin, Chlorin, and Ethyl Chlorophyllide a . Spangler, D., Maggiora, G.M., Shipman, L.L., and Christoffersen, R.E. J. Am. Chem. Soc . 99,7478–7489 (1977).

  22. Stereoelectronic Properties of Photosynthetic and Related Systems. Ground State Characterization of Free Base Porphin, Chlorin, and Ethyl Pheophorbide a. Spangler, D., Maggiora, G.M., Shipman, L.L., and Christoffersen, R.E. J. Am. Chem. Soc . 99, 7470–7477 (1977).

  23. Ab Initio Calculations on Large Molecules Using Molecular Fragments. Comparison of Charge Distributions and Molecular Electrostatic Potentials for Ethyl Chlorophyllide a and Related Molecules. Oie, T., Maggiora, G.M., and Christoffersen, R.E. Int. J. Quantum Chem.: Quantum Biol. Symp. No. 3 , pp. 119-130 (1976).

  24. Ab Initio Calculations on Large Molecules Using Molecular Fragments. Preliminary Investigations on Ethyl Chlorophyllide a and Related Molecules. Spangler, D., McKinney, R., Christoffersen, R.E., Maggiora, G.M., and Shipman, L.L. Chem. Phys. Letts . 36, 427–431 (1975).

  25. Electronic Structure of Porphyrins. III. All Valence-Electron SCF MO CI Calculations of the Excited Singlet States of Dianion and Free Base Reduced Porphins. Maggiora, G.M. and Weimann, L.J. Chem. Phys. Letts ., 22, 291–300 (1974).

  26. Electronic Structure of Porphyrins. All Valence-Electron SCF MO CI Calculations of the Spectra of Dianion and Free Base Porphin. Maggiora, G.M. and Weimann, L.J. Chem. Phys. Letts . 22, 291–300 (1973).

  27. Electronic Structure of Porphyrins. All Valence-Electron Self-Consistent Field Molecular Orbital Calculations of Free Base, Magnesium, and Aquo-magnesium Porphins. Maggiora, G.M. J. Am. Chem. Soc., 95, 6555–6559 (1973).

  28. Chlorophyll Triplet States – Some Theoretical Considerations on Triplet Formation. Maggiora, G.M. and Ingraham, L.L. In Structure and Bonding , C.K. Jorgensen and J.B. Neilands (Eds.). Springer-Verlag, Vol. II, pp. 126–159 (1967).

Proteins, Peptides, and Nucleic Acid Structure and Function

  1. Comparing Protein Structures: A Gaussian-Based Approach to Three-Dimensional Structure Similarity. Maggiora, G.M., Rohrer, D.C., and Mestres, J., J. Mol. Graphics Model ., 19, 168–178 (1999).

  2. A Molecular Field-Based Similarity Study of Non-Nucleoside HIV-1 Inhibitors. 2. The Relationship Between Alignment Solutions Obtained from Conformationally Rigid and Flexible Matching. Mestres, J., Rohrer, D.C., and Maggiora, G.M., J. Comput.-Aided Molec. Design, 14, 39–51 (1999).

  3. Gaussian-Based Approaches to Protein Structure Similarity. Mestres, J., Rohrer, D.C., and Maggiora, G.M. In Molecular Modeling and Prediction of Bioactivity .. K. Gundertofte and F.S. Jorgensen, Eds., Kluwer Academic Publishers, New York, pp. 83–8, 20008.

  4. Domain Structural Class Prediction. Chou, K.C. and Maggiora, G.M., Prot. Engineer., 11, 523–538 (1998).

  5. Disposition of Amphiphilic Helices in Heteropolar Environments. Chou, K.C., Zhang, C. T., and Maggiora, G. M.. Proteins , 28, 99–108 (1997).

  6. A Consensus Procedure for Predicting the Location of a-Helical Transmembrane Segments in Proteins. Parodi, L.A., Granatir, C. A., and Maggiora, G. M., CABIOS, 10, 527–535 (1994).

  7. Solitary Wave Dynamics as a Mechanism for Explaining the Internal Motion During Microtubule Growth. Chou, K.-C., Zhang, C.-T., and Maggiora, G. M. Biopolymers , 34, 143–153 (1993).

  8. The Role of Loop-Helix Interactions in Stabilizing Four-Helix Bundle Proteins. Chou, K.-C., Maggiora, G. M., and Scheraga, H. A., Proc. Natl. Acad. Sci. U.S.A. , 89, 7315–7319 (1992).

  9. An Energy-Based Approach to Packing the 7-Helix Bundle of Bacteriorhodopsin. Chou, K.-C., Carlacci, L., Parodi, L. A., Maggiora, G. M., and Schulz, M. W.. Prot. Sci ., 1, 810–827, (1992).

  10. Computer Modeling of Constrained Peptide Systems. Blinn, J. R., Chou, K.-C., Howe, W. J., Maggiora, G. M., Mao, B., and Moon, J. B. In The Role of Computational Models and Theories in Biotechnology , J. Bertran, Ed., Kluwer Scientific Publishers, The Netherlands, pp. 17–35 (1992).

  11. An Augmented Ribbon Model of Protein Structure. Nicholson, V. A. and Maggiora, G. M., J. Math. Chem., 11, 47–63 (1992).

  12. Mass-Weighted Molecular Dynamics Simulation of Cyclic Peptides. Mao, B., Maggiora, G. M., and Chou, K.-C., Biopolymers , 31, 1077–1086 (1991).

  13. A Heuristic Approach to Predicting the Tertiary Structure of Bovine Somatotropin. Carlacci, L., Chou, K.-C., and Maggiora, G. M. Biochemistry 30, 4389–4398, (1991).

  14. Predicting the Three-Dimensional Structures of Proteins by Homology-Based Model Building. Maggiora, G. M., Narasimhan, S. L., Granatir, C. A., Blinn, J. R., and Moon, J. B. Theoretical and Computational Models for Organic Chemistry , S. J. Formosinho et al., Eds., Kluwer Scientific Publishers, The Netherlands, pp. 137–158 (1991).

  15. Conformation and Geometrical Properties of Idealized ß-Barrels in Proteins. Chou, K.-C., Carlacci, L., and Maggiora, G. M. J. Mol. Biol . 213, 315–326 (1990).

  16. A New Chiral Feature in a-Helical Domains of Proteins. Maggiora, G. M., Mezey, P. G., Mao, B., and Chou, K.-C. Biopolymers 30, 211–214 (1990).

  17. Topological Analysis of Hydrogen Bonding in Proteins. Mao, B., Chou, K.-C., and Maggiora, G. M. Eur. J. Biochem. 188, 361–365 (1990).

  18. Theoretical and Empirical Approaches to Protein Structure Prediction and Analysis. Maggiora, G. M., Mao, B., Chou, K.-C., and Narasimhan, S.L. Methods of Biochemical Analysis , Volume 35, C. Seulter, Ed., Academic Press, Orlando, Florida, pp. 1–86 (1990).

  19. Chiral Features of Proteins. Maggiora, G. M., Mao, B., and Chou, K.-C. In New Directions in Molecular Chirality , P. G. Mezey, Ed., Kluwer Scientific Publishers, pp. 93–118 (1990).

  20. Quasi-Continuum Models of Twist-Like and Accordion-Like Motions in DNA. Chou, K.-C., Maggiora, G. M., and Mao, B. Biophys. J . 56, 295–305 (1989).

  21. Energetics of the Structure of the Four-a-helix Bundle in Proteins. Chou, K.-C., Maggiora, G. M., Nemethy, G., and Scheraga, H. A. Proc. Nat. Acad. Sci. (USA) 85, 4295–4299 (1988).

  22. Biological Functions of Low Frequency Vibrations (Phonons): 7. The Impetus for DNA to Accommodate Intercalators. Chou, K.-C. and Maggiora, G. M. British Polymer Journal 20, 143–148 (1988).

Set-theoretical Applications — Classical, Fuzzy, and Rough Sets

  1. Set-Theoretic Formalism for Treating Ligand-Target Datasets. Maggiora, G.M. and Vogt, M. Molecules 26, 7419 (23 pages). https://doi.org/10.3390/molecules26247419.

  2. An Intuitionistic Fuzzy Set Analysis of Drug-Target Interactions. Maggiora, G.M. and Szmidt, E. MATCH, Communications in Mathematical and Computer Chemistry 85, 465–468 (2021).

  3. A Rough Set Theory Approach to the Analysis of Gene Expression Profiles. Petit, J., Meurice, N., Medina-Franco, J.L. and Maggiora, G.M. In Chemoinformatics for Drug Discovery , J. Bajorath, Ed., John Wiley & Sons, New York, pp. 51–83 (2014).

  4. Rough Set Theory as an Interpretable Method for Predicting the Inhibition of Cytochrome P450 1A2 and 2D6. Burton, J., Petit, J., Danloy, E., Maggiora, G.M., and Vercauteren, D.P. Mol. Inf. 32, 579–589 (2013).

  5. Predicting Protein Structural Classes from Amino Acid Composition: Application of Fuzzy Clustering. Zhang, C.T., Chou, K.C., and Maggiora, G.M., Prot. Engineer ., 8, 425–435 (1994).

  6. Combining Fuzzy Clustering and Neural Networks to Classify Protein Structural Families. Maggiora, G.M., Zhang, C.T., Chou, K.C. and Elrod, D.W. Neural Networks in QSAR and Drug Design, J. Devillers, Ed., Academic Press, London, pp. 255–279 (1996).

  7. A Fuzzy Set Approach to Functional Group Comparisons Based on an Asymmetric Similarity Measure. Maggiora, G.M. and Mezey, P. Int. J. Quantum Chem. 74, 503–514 (1998).

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Acknowledgements

I would like to thank John Van Drie, Linda Restifo, and José Medina-Franco for reading the manuscript and for their very helpful and insightful comments, which have materially improved this work.

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    Gerry Maggiora

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Maggiora, G. Is the reductionist paradox an Achilles Heel of drug discovery?. J Comput Aided Mol Des 36, 329–338 (2022). https://doi.org/10.1007/s10822-022-00457-2

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