Protein Flexibility in Docking-Based Virtual Screening: Discovery of Novel Lymphoid-Specific Tyrosine Phosphatase Inhibitors Using Multiple Crystal Structures

Journal of Chemical Information and Modeling

Volumn 55, Issue 9, 2015, Pages 1973-1983

  Hou, Xuben ^a   Li, Kangshuai ^b   Yu, Xiao ^b   Sun, Jin Peng ^b   Fang, Hao ^a  

^a SHANDONG UNIVERSITY   (China)

^b SHANDONG UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; CELL MEMBRANES; CELL SIGNALING; CRYSTALS; PHOSPHATASES; T-CELLS;

AUTOIMMUNE DISEASE; POTENTIAL DRUG TARGETS; PROTEIN CONFORMATION; PROTEIN FLEXIBILITY; PROTEIN PHOSPHATASE; PROTEIN STRUCTURES; THERAPEUTIC AGENTS; TYROSINE PHOSPHATASE;

DIAGNOSIS;

ENZYME INHIBITOR; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 22; PROTEIN BINDING; PTPN22 PROTEIN, HUMAN;

ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; CHEMISTRY; DRUG DEVELOPMENT; IC50; MOLECULAR DYNAMICS; PRECLINICAL STUDY; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; INHIBITORY CONCENTRATION 50; MODELS, BIOLOGICAL; MOLECULAR DYNAMICS SIMULATION; PROTEIN BINDING; PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 22;

EID: 84942515430     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/acs.jcim.5b00344     Document Type: Article

References (84)

1. Brooijmans, N.; Kuntz, I. D. Molecular Recognition and Docking Algorithms Annu. Rev. Biophys. Biomol. Struct. 2003, 32, 335-373 10.1146/annurev.biophys.32.110601.142532
2. Hermann, J. C.; Marti-Arbona, R.; Fedorov, A. A.; Fedorov, E.; Almo, S. C.; Shoichet, B. K.; Raushel, F. M. Structure-Based Activity Prediction for an Enzyme of Unknown Function Nature 2007, 448, 775-779 10.1038/nature05981
3. Chen, Y. C. Beware of Docking! Trends Pharmacol. Sci. 2015, 36, 78-95 10.1016/j.tips.2014.12.001
4. Shoichet, B. K. Virtual Screening of Chemical Libraries Nature 2004, 432, 862-865 10.1038/nature03197
5. Zhuang, C. L.; Narayanapillai, S.; Zhang, W. N.; Sham, Y. Y.; Xing, C. G. Rapid Identification of Keap1-Nrf2 Small-Molecule Inhibitors through Structure-Based Virtual Screening and Hit-Based Substructure Search J. Med. Chem. 2014, 57, 1121-1126 10.1021/jm4017174
6. Ripphausen, P.; Nisius, B.; Peltason, L.; Bajorath, J. Quo Vadis, Virtual Screening? A Comprehensive Survey of Prospective Applications J. Med. Chem. 2010, 53, 8461-8467 10.1021/jm101020z
7. Hou, X. B.; Du, J. T.; Zhang, J.; Du, L. P.; Fang, H.; Li, M. Y. How to Improve Docking Accuracy of Autodock4.2: A Case Study Using Different Electrostatic Potentials J. Chem. Inf. Model. 2013, 53, 188-200 10.1021/ci300417y
8. Santos-Martins, D.; Forli, S.; Ramos, M. J.; Olson, A. J. Autodock4(Zn): An Improved Autodock Force Field for Small-Molecule Docking to Zinc Metalloproteins J. Chem. Inf. Model. 2014, 54, 2371-2379 10.1021/ci500209e
9. Morris, G. M.; Huey, R.; Lindstrom, W.; Sanner, M. F.; Belew, R. K.; Goodsell, D. S.; Olson, A. J. Autodock4 and Autodocktools4: Automated Docking with Selective Receptor Flexibility J. Comput. Chem. 2009, 30, 2785-2791 10.1002/jcc.21256
10. Lang, P. T.; Brozell, S. R.; Mukherjee, S.; Pettersen, E. F.; Meng, E. C.; Thomas, V.; Rizzo, R. C.; Case, D. A.; James, T. L.; Kuntz, I. D. Dock 6: Combining Techniques to Model Rna-Small Molecule Complexes RNA 2009, 15, 1219-1230 10.1261/rna.1563609
11. Moustakas, D. T.; Lang, P. T.; Pegg, S.; Pettersen, E.; Kuntz, I. D.; Brooijmans, N.; Rizzo, R. C. Development and Validation of a Modular, Extensible Docking Program: Dock 5 J. Comput.-Aided Mol. Des. 2006, 20, 601-619 10.1007/s10822-006-9060-4
12. Verdonk, M. L.; Chessari, G.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.; Nissink, J. W. M.; Taylor, R. D.; Taylor-, R. Modeling Water Molecules in Protein-Ligand Docking Using Gold J. Med. Chem. 2005, 48, 6504-6515 10.1021/jm050543p
13. Verdonk, M. L.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.; Taylor, R. D. Improved Protein-Ligand Docking Using Gold Proteins: Struct., Funct., Genet. 2003, 52, 609-623 10.1002/prot.10465
14. Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shelley, M.; Perry, J. K.; Shaw, D. E.; Francis, P.; Shenkin, P. S. Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking Accuracy J. Med. Chem. 2004, 47, 1739-1749 10.1021/jm0306430
15. Halgren, T. A.; Murphy, R. B.; Friesner, R. A.; Beard, H. S.; Frye, L. L.; Pollard, W. T.; Banks, J. L. Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening J. Med. Chem. 2004, 47, 1750-1759 10.1021/jm030644s
16. Jain, A. N. Surflex-Dock 2.1: Robust Performance from Ligand Energetic Modeling, Ring Flexibility, and Knowledge-Based Search J. Comput.-Aided Mol. Des. 2007, 21, 281-306 10.1007/s10822-007-9114-2
17. Kramer, B.; Rarey, M.; Lengauer, T. Evaluation of the Flexx Incremental Construction Algorithm for Protein-Ligand Docking Proteins: Struct., Funct., Genet. 1999, 37, 228-241 10.1002/(SICI)1097-0134(19991101)37:2<228::AID-PROT8>3.0.CO;2-8
18. Plewczynski, D.; Lazniewski, M.; Von Grotthuss, M.; Rychlewski, L.; Ginalski, K. Votedock: Consensus Docking Method for Prediction of Protein-Ligand Interactions J. Comput. Chem. 2011, 32, 568-581 10.1002/jcc.21642
19. Cavasotto, C. N.; Abagyan, R. A. Protein Flexibility in Ligand Docking and Virtual Screening to Protein Kinases J. Mol. Biol. 2004, 337, 209-225 10.1016/j.jmb.2004.01.003
20. B-Rao, C.; Subramanian, J.; Sharma, S. D. Managing Protein Flexibility in Docking and Its Applications Drug Discovery Today 2009, 14, 394-400 10.1016/j.drudis.2009.01.003
21. Therrien, E.; Weill, N.; Tomberg, A.; Corbeil, C. R.; Lee, D.; Moitessier, N. Docking Ligands into Flexible and Solvated Macromolecules. 7. Impact of Protein Flexibility and Water Molecules on Docking-Based Virtual Screening Accuracy J. Chem. Inf. Model. 2014, 54, 3198-3210 10.1021/ci500299h
22. Fischer, M.; Coleman, R. G.; Fraser, J. S.; Shoichet, B. K. Incorporation of Protein Flexibility and Conformational Energy Penalties in Docking Screens to Improve Ligand Discovery Nat. Chem. 2014, 6, 575-583 10.1038/nchem.1954
23. Alberts, I. L.; Todorov, N. P.; Dean, P. M. Receptor Flexibility in De Novo Ligand Design and Docking J. Med. Chem. 2005, 48, 6585-6596 10.1021/jm050196j
24. Schmeing, T. M.; Huang, K. S.; Strobel, S. A.; Steitz, T. A. An Induced-Fit Mechanism to Promote Peptide Bond Formation and Exclude Hydrolysis of Peptidyl-Trna Nature 2005, 438, 520-524 10.1038/nature04152
25. Williamson, J. R. Induced Fit in Rna-Protein Recognition Nat. Struct. Biol. 2000, 7, 834-837 10.1038/79575
26. Koshland, D. E. The Key-Lock Theory and the Induced Fit Theory Angew. Chem., Int. Ed. Engl. 1995, 33, 2375-2378 10.1002/anie.199423751
27. Salsbury, F. R., Jr. Molecular Dynamics Simulations of Protein Dynamics and Their Relevance to Drug Discovery Curr. Opin. Pharmacol. 2010, 10, 738-744 10.1016/j.coph.2010.09.016
28. Borhani, D. W.; Shaw, D. E. The Future of Molecular Dynamics Simulations in Drug Discovery J. Comput.-Aided Mol. Des. 2012, 26, 15-26 10.1007/s10822-011-9517-y
29. Durrant, J. D.; McCammon, J. A. Molecular Dynamics Simulations and Drug Discovery BMC Biol. 2011, 9, 71 10.1186/1741-7007-9-71
30. Flick, J.; Tristram, F.; Wenzel, W. Modeling Loop Backbone Flexibility in Receptor-Ligand Docking Simulations J. Comput. Chem. 2012, 33, 2504-2515 10.1002/jcc.23087
31. Tian, S.; Sun, H. Y.; Pan, P. C.; Li, D.; Zhen, X. C.; Li, Y. Y.; Hou, T. J. Assessing an Ensemble Docking-Based Virtual Screening Strategy for Kinase Targets by Considering Protein Flexibility J. Chem. Inf. Model. 2014, 54, 2664-2679 10.1021/ci500414b
32. Craig, I. R.; Essex, J. W.; Spiegel, K. Ensemble Docking into Multiple Crystallographically Derived Protein Structures: An Evaluation Based on the Statistical Analysis of Enrichments J. Chem. Inf. Model. 2010, 50, 511-524 10.1021/ci900407c
33. Huang, S. Y.; Zou, X. Q. Ensemble Docking of Multiple Protein Structures: Considering Protein Structural Variations in Molecular Docking Proteins: Struct., Funct., Genet. 2007, 66, 399-421 10.1002/prot.21214
34. Li, Y.; Kim, D. J.; Ma, W. Y.; Lubet, R. A.; Bode, A. M.; Dong, Z. G. Discovery of Novel Checkpoint Kinase 1 Inhibitors by Virtual Screening Based on Multiple Crystal Structures J. Chem. Inf. Model. 2011, 51, 2904-2914 10.1021/ci200257b
35. Mahasenan, K. V.; Li, C. L. Novel Inhibitor Discovery through Virtual Screening against Multiple Protein Conformations Generated Via Ligand-Directed Modeling: A Maternal Embryonic Leucine Zipper Kinase Example J. Chem. Inf. Model. 2012, 52, 1345-1355 10.1021/ci300040c
36. Wang, L.; Gu, Q.; Zheng, X. H.; Ye, J. M.; Liu, Z. H.; Li, J. B.; Hu, X. P.; Hagler, A.; Xu, J. Discovery of New Selective Human Aldose Reductase Inhibitors through Virtual Screening Multiple Binding Pocket Conformations J. Chem. Inf. Model. 2013, 53, 2409-2422 10.1021/ci400322j
37. Tian, S.; Sun, H. Y.; Li, Y. Y.; Pan, P. C.; Li, D.; Hou, T. J. Development and Evaluation of an Integrated Virtual Screening Strategy by Combining Molecular Docking and Pharmacophore Searching Based on Multiple Protein Structures J. Chem. Inf. Model. 2013, 53, 2743-2756 10.1021/ci400382r
38. Korb, O.; Olsson, T. S. G.; Bowden, S. J.; Hall, R. J.; Verdonk, M. L.; Liebeschuetz, J. W.; Cole, J. C. Potential and Limitations of Ensemble Docking J. Chem. Inf. Model. 2012, 52, 1262-1274 10.1021/ci2005934
39. Alonso, A.; Sasin, J.; Bottini, N.; Friedberg, I.; Osterman, A.; Godzik, A.; Hunter, T.; Dixon, J.; Mustelin, T. Protein Tyrosine Phosphatases in the Human Genome Cell 2004, 117, 699-711 10.1016/j.cell.2004.05.018
40. Bottini, N.; Peterson, E. J. Tyrosine Phosphatase Ptpn22: Multifunctional Regulator of Immune Signaling, Development, and Disease Annu. Rev. Immunol. 2014, 32, 83-119 10.1146/annurev-immunol-032713-120249
41. Bottini, N.; Musumeci, L.; Alonso, A.; Rahmouni, S.; Nika, K.; Rostamkhani, M.; MacMurray, J.; Meloni, G. F.; Lucarelli, P.; Pellecchia, M.; Eisenbarth, G. S.; Comings, D.; Mustelin, T. A Functional Variant of Lymphoid Tyrosine Phosphatase Is Associated with Type I Diabetes Nat. Genet. 2004, 36, 337-338 10.1038/ng1323
42. Vang, T.; Liu, W. H.; Delacroix, L.; Wu, S.; Vasile, S.; Dahl, R.; Yang, L.; Musumeci, L.; Francis, D.; Landskron, J.; Tasken, K.; Tremblay, M. L.; Lie, B. A.; Page, R.; Mustelin, T.; Rahmouni, S.; Rickert, R. C.; Tautz, L. Lyp Inhibits T-Cell Activation When Dissociated from Csk Nat. Chem. Biol. 2012, 8, 437-446 10.1038/nchembio.916
43. Hou, X. B.; Li, R.; Li, K. S.; Yu, X.; Sun, J. P.; Fang, H. Fast Identification of Novel Lymphoid Tyrosine Phosphatase Inhibitors Using Target-Ligand Interaction-Based Virtual Screening J. Med. Chem. 2014, 57, 9309-9322 10.1021/jm500692u
44. Vang, T.; Congia, M.; Macis, M. D.; Musumeci, L.; Orru, V.; Zavattari, P.; Nika, K.; Tautz, L.; Tasken, K.; Cucca, F.; Mustelin, T.; Bottini, N. Autoimmune-Associated Lymphoid Tyrosine Phosphatase Is a Gain-of-Function Variant Nat. Genet. 2005, 37, 1317-1319 10.1038/ng1673
45. He, Y. T.; Liu, S. J.; Menon, A.; Stanford, S.; Oppong, E.; Gunawan, A. M.; Wu, L.; Wu, D. J.; Barrios, A. M.; Bottini, N.; Cato, A. C. B.; Zhang, Z. Y. A Potent and Selective Small-Molecule Inhibitor for the Lymphoid-Specific Tyrosine Phosphatase (Lyp), a Target Associated with Autoimmune Diseases J. Med. Chem. 2013, 56, 4990-5008 10.1021/jm400248c
46. Yu, X.; Sun, J. P.; He, Y. T.; Guo, X. L.; Liu, S. J.; Zhou, B.; Hudmon, A.; Zhang, Z. Y. Structure, Inhibitor, and Regulatory Mechanism of Lyp, a Lymphoid-Specific Tyrosine Phosphatase Implicated in Autoimmune Diseases Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 19767-19772 10.1073/pnas.0706233104
47. Liu, G.; Xin, Z. L.; Liang, H.; Abad-Zapatero, C.; Hajduk, P. J.; Janowick, D. A.; Szczepankiewicz, B. G.; Pei, Z. H.; Hutchins, C. W.; Ballaron, S. J.; Stashko, M. A.; Lubben, T. H.; Berg, C. E.; Rondinone, C. M.; Trevillyan, J. M.; Jirousek, M. R. Selective Protein Tyrosine Phosphatase 1b Inhibitors: Targeting the Second Phosphotyrosine Binding Site with Non-Carboxylic Acid-Containing Ligands J. Med. Chem. 2003, 46, 3437-3440 10.1021/jm034088d
48. Sheriff, S.; Beno, B. R.; Zhai, W. X.; Kostich, W. A.; McDonnell, P. A.; Kish, K.; Goldfarb, V.; Gao, M. A.; Kiefer, S. E.; Yanchunas, J.; Huang, Y. L.; Shi, S. H.; Zhu, S. R.; Dzierba, C.; Bronson, J.; Macor, J. E.; Appiah, K. K.; Westphal, R. S.; O'Connell, J.; Gerritz, S. W. Small Molecule Receptor Protein Tyrosine Phosphatase Gamma (Rptp Gamma) Ligands That Inhibit Phosphatase Activity Via Perturbation of the Tryptophan-Proline-Aspartate (Wpd) Loop J. Med. Chem. 2011, 54, 6548-6562 10.1021/jm2003766
49. Cui, W.; Cheng, Y. H.; Geng, L. L.; Liang, D. S.; Hou, T. J.; Ji, M. J. Unraveling the Allosteric Inhibition Mechanism of Ptp1b by Free Energy Calculation Based on Umbrella Sampling J. Chem. Inf. Model. 2013, 53, 1157-1167 10.1021/ci300526u
50. Wu, S. D.; Bottini, M.; Rickert, R. C.; Mustelin, T.; Tautz, L. In Silico Screening for Ptpn22 Inhibitors: Active Hits from an Inactive Phosphatase Conformation ChemMedChem 2009, 4, 440-444 10.1002/cmdc.200800375
51. Barril, X.; Morley, S. D. Unveiling the Full Potential of Flexible Receptor Docking Using Multiple Crystallographic Structures J. Med. Chem. 2005, 48, 4432-4443 10.1021/jm048972v
52. Rueda, M.; Bottegoni, G.; Abagyan, R. Recipes for the Selection of Experimental Protein Conformations for Virtual Screening J. Chem. Inf. Model. 2010, 50, 186-193 10.1021/ci9003943
53. Venkatraman, V.; Perez-Nueno, V. I.; Mavridis, L.; Ritchie, D. W. Comprehensive Comparison of Ligand-Based Virtual Screening Tools against the Dud Data Set Reveals Limitations of Current 3d Methods J. Chem. Inf. Model. 2010, 50, 2079-2093 10.1021/ci100263p
54. Mysinger, M. M.; Carchia, M.; Irwin, J. J.; Shoichet, B. K. Directory of Useful Decoys, Enhanced (Dud-E): Better Ligands and Decoys for Better Benchmarking J. Med. Chem. 2012, 55, 6582-6594 10.1021/jm300687e
55. Kao, R. Y. T.; Jenkins, J. L.; Olson, K. A.; Key, M. E.; Fett, J. W.; Shapiro, R. A Small-Molecule Inhibitor of the Ribonucleolytic Activity of Human Angiogenin That Possesses Antitumor Activity Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 10066-10071 10.1073/pnas.152342999
56. Jenkins, J. L.; Kao, R. Y. T.; Shapiro, R. Virtual Screening to Enrich Hit Lists from High-Throughput Screening: A Case Study on Small-Molecule Inhibitors of Angiogenin Proteins: Struct., Funct., Genet. 2003, 50, 81-93 10.1002/prot.10270
57. Maggiora, G.; Vogt, M.; Stumpfe, D.; Bajorath, J. Molecular Similarity in Medicinal Chemistry J. Med. Chem. 2014, 57, 3186-3204 10.1021/jm401411z
58. Salim, N.; Holliday, J.; Willett, P. Combination of Fingerprint-Based Similarity Coefficients Using Data Fusion J. Chem. Inf. Model. 2003, 43, 435-442 10.1021/ci025596j
59. Baell, J. B.; Holloway, G. A. New Substructure Filters for Removal of Pan Assay Interference Compounds (Pains) from Screening Libraries and for Their Exclusion in Bioassays J. Med. Chem. 2010, 53, 2719-2740 10.1021/jm901137j
60. Dimova, D.; Hu, Y.; Bajorath, J. Matched Molecular Pair Analysis of Small Molecule Microarray Data Identifies Promiscuity Cliffs and Reveals Molecular Origins of Extreme Compound Promiscuity J. Med. Chem. 2012, 55, 10220-10228 10.1021/jm301292a
61. Hu, Y.; Bajorath, J. Growth of Ligand-Target Interaction Data in Chembl Is Associated with Increasing and Activity Measurement-Dependent Compound Promiscuity J. Chem. Inf. Model. 2012, 52, 2550-2558 10.1021/ci3003304
62. Mendgen, T.; Steuer, C.; Klein, C. D. Privileged Scaffolds or Promiscuous Binders: A Comparative Study on Rhodanines and Related Heterocycles in Medicinal Chemistry J. Med. Chem. 2012, 55, 743-753 10.1021/jm201243p
63. Erbe, D. V.; Wang, S.; Zhang, Y. L.; Harding, K.; Kung, L.; Tam, M.; Stolz, L.; Xing, Y.; Furey, S.; Qadri, A.; Klaman, L. D.; Tobin, J. F. Ertiprotafib Improves Glycemic Control and Lowers Lipids Via Multiple Mechanisms Mol. Pharmacol. 2005, 67, 69-77 10.1124/mol.104.005553
64. Cousin, D.; Mann, J.; Nieuwenhuyzen, M.; van den Berg, H. A New Approach to Combretastatin D2 Org. Biomol. Chem. 2006, 4, 54 10.1039/B513515J
65. Barr, A. J.; Ugochukwu, E.; Lee, W. H.; King, O. N.; Filippakopoulos, P.; Alfano, I.; Savitsky, P.; Burgess-Brown, N. A.; Muller, S.; Knapp, S. Large-Scale Structural Analysis of the Classical Human Protein Tyrosine Phosphatome Cell 2009, 136, 352-363 10.1016/j.cell.2008.11.038
66. Stanford, S. M.; Krishnamurthy, D.; Falk, M. D.; Messina, R.; Debnath, B.; Li, S.; Liu, T.; Kazemi, R.; Dahl, R.; He, Y. T.; Yu, X. A.; Chan, A. C.; Zhang, Z. Y.; Barrios, A. M.; Woods, V. L.; Neamati, N.; Bottini, N. Discovery of a Novel Series of Inhibitors of Lymphoid Tyrosine Phosphatase with Activity in Human T Cells J. Med. Chem. 2011, 54, 1640-1654 10.1021/jm101202j
67. Pronk, S.; Pall, S.; Schulz, R.; Larsson, P.; Bjelkmar, P.; Apostolov, R.; Shirts, M. R.; Smith, J. C.; Kasson, P. M.; van der Spoel, D.; Hess, B.; Lindahl, E. Gromacs 4.5: A High-Throughput and Highly Parallel Open Source Molecular Simulation Toolkit Bioinformatics 2013, 29, 845-854 10.1093/bioinformatics/btt055
68. Van der Spoel, D.; Lindahl, E.; Hess, B.; Groenhof, G.; Mark, A. E.; Berendsen, H. J. C. Gromacs: Fast, Flexible, and Free J. Comput. Chem. 2005, 26, 1701-1718 10.1002/jcc.20291
69. Lindorff-Larsen, K.; Piana, S.; Palmo, K.; Maragakis, P.; Klepeis, J. L.; Dror, R. O.; Shaw, D. E. Improved Side-Chain Torsion Potentials for the Amber Ff99sb Protein Force Field Proteins: Struct., Funct., Genet. 2010, 78, 1950-1958 10.1002/prot.22711
70. Mark, P.; Nilsson, L. Structure and Dynamics of the Tip3p, Spc, and Spc/E Water Models at 298 K J. Phys. Chem. A 2001, 105, 9954-9960 10.1021/jp003020w
71. Cerutti, D. S.; Duke, R. E.; Darden, T. A.; Lybrand, T. P. Staggered Mesh Ewald: An Extension of the Smooth Particle-Mesh Ewald Method Adding Great Versatility J. Chem. Theory Comput. 2009, 5, 2322-2338 10.1021/ct9001015
72. Hess, B. P-Lincs: A Parallel Linear Constraint Solver for Molecular Simulation J. Chem. Theory Comput. 2008, 4, 116-122 10.1021/ct700200b
73. Wang, J. M.; Wang, W.; Kollman, P. A.; Case, D. A. Automatic Atom Type and Bond Type Perception in Molecular Mechanical Calculations J. Mol. Graphics Modell. 2006, 25, 247-260 10.1016/j.jmgm.2005.12.005
74. Wang, J. M.; Wolf, R. M.; Caldwell, J. W.; Kollman, P. A.; Case, D. A. Development and Testing of a General Amber Force Field J. Comput. Chem. 2004, 25, 1157-1174 10.1002/jcc.20035
75. Jakalian, A.; Jack, D. B.; Bayly, C. I. Fast, Efficient Generation of High-Quality Atomic Charges. Am1-Bcc Model: Ii. Parameterization and Validation J. Comput. Chem. 2002, 23, 1623-1641 10.1002/jcc.10128
76. Jakalian, A.; Bush, B. L.; Jack, D. B.; Bayly, C. I. Fast, Efficient Generation of High-Quality Atomic Charges. Am1-Bcc Model: I. Method J. Comput. Chem. 2000, 21, 132-146 10.1002/(SICI)1096-987X(20000130)21:2<132::AID-JCC5>3.0.CO;2-P
77. Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.; Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. Ucsf Chimera-a Visualization System for Exploratory Research and Analysis J. Comput. Chem. 2004, 25, 1605-1612 10.1002/jcc.20084
78. Hou, X.; Du, J.; Liu, R.; Zhou, Y.; Li, M.; Xu, W.; Fang, H. Enhancing the Sensitivity of Pharmacophore-Based Virtual Screening by Incorporating Customized Zbg Features: A Case Study Using Histone Deacetylase 8 J. Chem. Inf. Model. 2015, 55, 861-871 10.1021/ci500762z
79. Yu, X.; Sun, J. P.; He, Y.; Guo, X.; Liu, S.; Zhou, B.; Hudmon, A.; Zhang, Z. Y. Structure, Inhibitor, and Regulatory Mechanism of Lyp, a Lymphoid-Specific Tyrosine Phosphatase Implicated in Autoimmune Diseases Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 19767-19772 10.1073/pnas.0706233104
80. Liu, J.; Chen, M.; Li, R.; Yang, F.; Shi, X.; Zhu, L.; Wang, H. M.; Yao, W.; Liu, Q.; Meng, F. G.; Sun, J. P.; Pang, Q.; Yu, X. Biochemical and Functional Studies of Lymphoid-Specific Tyrosine Phosphatase (Lyp) Variants S201f and R266w PLoS One 2012, 7, e43631 10.1371/journal.pone.0043631
81. Huijbers, I. J.; Bin Ali, R.; Pritchard, C.; Cozijnsen, M.; Kwon, M. C.; Proost, N.; Song, J. Y.; de Vries, H.; Badhai, J.; Sutherland, K.; Krimpenfort, P.; Michalak, E. M.; Jonkers, J.; Berns, A. Rapid Target Gene Validation in Complex Cancer Mouse Models Using Re-Derived Embryonic Stem Cells EMBO Mol. Med. 2014, 6, 212-225 10.1002/emmm.201303297
82. Gloria-Bottini, F.; Ammendola, M.; Saccucci, P.; Pietropolli, A.; Magrini, A.; Bottini, E. The Association of Ptpn22 Polymorphism with Endometriosis: Effect of Genetic and Clinical Factors Eur. J. Obstet. Gynecol. Reprod. Biol. 2013, 169, 60-63 10.1016/j.ejogrb.2013.01.014
83. Pan, C.; Liu, H. D.; Gong, Z.; Yu, X.; Hou, X. B.; Xie, D. D.; Zhu, X. B.; Li, H. W.; Tang, J. Y.; Xu, Y. F.; Yu, J. Q.; Zhang, L. Y.; Fang, H.; Xiao, K. H.; Chen, Y. G.; Wang, J. Y.; Pang, Q.; Chen, W.; Sun, J. P. Cadmium Is a Potent Inhibitor of Ppm Phosphatases and Targets the M1 Binding Site Sci. Rep. 2013, 3, 2333 10.1038/srep02333
84. Sun, J. P.; Fedorov, A. A.; Lee, S. Y.; Guo, X. L.; Shen, K.; Lawrence, D. S.; Almo, S. C.; Zhang, Z. Y. Crystal Structure of Ptp1b Complexed with a Potent and Selective Bidentate Inhibitor J. Biol. Chem. 2003, 278, 12406-12414 10.1074/jbc.M212491200