The same is true for modeling and science in general. If the used method is not good,
if protein structures are not adequate, or the ligands are not properly processed, one
cannot obtain good data.
Compliance with Ethical Standards
Conflict of Interest: The author declares that he has no conflict of interest.
Funding: The author received no external funding during the preparation of this manuscript.
Ethical Approval: This article does not contain any studies with human participants or animals
performed by the author.
Informed Consent: This article does not contain any studies which required DNA samples.
References
1. Fry DC, Kuby SA, Mildvan AS (1985) NMR studies of the MgATP binding site of adenylate
kinase and of a 45-residue peptide fragment of the enzyme. Biochemistry 24:4680–4694.
https://doi.org/10.1021/bi00338a030
2. Taylor SS, Kornev AP (2010) Protein kinases: evolution of dynamic regulatory proteins. Trends
Biochem Sci 36:65–77. https://doi.org/10.1016/j.tibs.2010.09.006
3. Cramer RD, Patterson DE, Bunce JD (1988) Comparative molecular field analysis (CoMFA).
1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110:5959–5967.
https://doi.org/10.1021/ja00226a005
4. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N (2010) RAF inhibitors transactivate
RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 464:427–430. https://
doi.org/10.1038/nature08902
5. Durrant DE, Morrison DK (2017) Targeting the Raf kinases in human cancer: the Raf dimer
dilemma. Br J Cancer 118:3–8. https://doi.org/10.1038/bjc.2017.399
6. Wood ER, Truesdale AT, McDonald OB, Yuan D, Hassell A, Dickerson SH, Ellis B, Pennisi C,
Horne E, Lackey K, Alligood KJ, Rusnak DW, Gilmer TM, Shewchuk L (2004) A unique
structure for epidermal growth factor receptor bound to GW572016 (Lapatinib). Cancer Res
64:6652–6659. https://doi.org/10.1158/0008-5472.can-04-1168
7. Asquith CRM, Tizzard GJ, Bennett JM, Wells CI, Elkins JM, Willson TM, Poso A, Laitinen T
(2020) Targeting the water network in cyclin G associated kinase (GAK) with 4-anilino-quin
(az)oline inhibitors. ChemMedChem 15(13):1200–1215. https://doi.org/10.1002/cmdc.
202000150
8. Hansch C, Fujita T (1964) p-σ-π analysis. A method for the correlation of biological activity and
chemical structure. J Am Chem Soc 86:1616–1626. https://doi.org/10.1021/ja01062a035
9. Meng EC, Shoichet BK, Kuntz ID (1992) Automated docking with grid-based energy evaluation. J Comput Chem 13:505–524. https://doi.org/10.1002/jcc.540130412
10. Roskoski R (2016) Classification of small molecule protein kinase inhibitors based upon the
structures of their drug-enzyme complexes. Pharmacol Res 103:26–48. https://doi.org/10.1016/
j.phrs.2015.10.021
11. Martz KE, Dorn A, Baur B, Schattel V, Goettert MI, Mayer-Wrangowski SC, Rauh D, Laufer
SA (2012) Targeting the hinge glycine flip and the activation loop: novel approach to potent
p38α inhibitors. J Med Chem 55:7852. https://doi.org/10.1021/jm300951u
12. Pantsar T, Poso A (2018) Binding affinity via docking: fact and fiction. Molecules 23:1899.
https://doi.org/10.3390/molecules23081899
Molecular Modeling of Protein Kinases: Current Status and Challenges
37
if protein structures are not adequate, or the ligands are not properly processed, one
cannot obtain good data.
Compliance with Ethical Standards
Conflict of Interest: The author declares that he has no conflict of interest.
Funding: The author received no external funding during the preparation of this manuscript.
Ethical Approval: This article does not contain any studies with human participants or animals
performed by the author.
Informed Consent: This article does not contain any studies which required DNA samples.
References
1. Fry DC, Kuby SA, Mildvan AS (1985) NMR studies of the MgATP binding site of adenylate
kinase and of a 45-residue peptide fragment of the enzyme. Biochemistry 24:4680–4694.
https://doi.org/10.1021/bi00338a030
2. Taylor SS, Kornev AP (2010) Protein kinases: evolution of dynamic regulatory proteins. Trends
Biochem Sci 36:65–77. https://doi.org/10.1016/j.tibs.2010.09.006
3. Cramer RD, Patterson DE, Bunce JD (1988) Comparative molecular field analysis (CoMFA).
1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110:5959–5967.
https://doi.org/10.1021/ja00226a005
4. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N (2010) RAF inhibitors transactivate
RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 464:427–430. https://
doi.org/10.1038/nature08902
5. Durrant DE, Morrison DK (2017) Targeting the Raf kinases in human cancer: the Raf dimer
dilemma. Br J Cancer 118:3–8. https://doi.org/10.1038/bjc.2017.399
6. Wood ER, Truesdale AT, McDonald OB, Yuan D, Hassell A, Dickerson SH, Ellis B, Pennisi C,
Horne E, Lackey K, Alligood KJ, Rusnak DW, Gilmer TM, Shewchuk L (2004) A unique
structure for epidermal growth factor receptor bound to GW572016 (Lapatinib). Cancer Res
64:6652–6659. https://doi.org/10.1158/0008-5472.can-04-1168
7. Asquith CRM, Tizzard GJ, Bennett JM, Wells CI, Elkins JM, Willson TM, Poso A, Laitinen T
(2020) Targeting the water network in cyclin G associated kinase (GAK) with 4-anilino-quin
(az)oline inhibitors. ChemMedChem 15(13):1200–1215. https://doi.org/10.1002/cmdc.
202000150
8. Hansch C, Fujita T (1964) p-σ-π analysis. A method for the correlation of biological activity and
chemical structure. J Am Chem Soc 86:1616–1626. https://doi.org/10.1021/ja01062a035
9. Meng EC, Shoichet BK, Kuntz ID (1992) Automated docking with grid-based energy evaluation. J Comput Chem 13:505–524. https://doi.org/10.1002/jcc.540130412
10. Roskoski R (2016) Classification of small molecule protein kinase inhibitors based upon the
structures of their drug-enzyme complexes. Pharmacol Res 103:26–48. https://doi.org/10.1016/
j.phrs.2015.10.021
11. Martz KE, Dorn A, Baur B, Schattel V, Goettert MI, Mayer-Wrangowski SC, Rauh D, Laufer
SA (2012) Targeting the hinge glycine flip and the activation loop: novel approach to potent
p38α inhibitors. J Med Chem 55:7852. https://doi.org/10.1021/jm300951u
12. Pantsar T, Poso A (2018) Binding affinity via docking: fact and fiction. Molecules 23:1899.
https://doi.org/10.3390/molecules23081899
Molecular Modeling of Protein Kinases: Current Status and Challenges
37