An Exploration of Human D-Crystallin Affinity for Potential Aggregation Inhibitors: A Molecular Docking Investigation
DOI:
https://doi.org/10.24193/subbchem.2024.3.05Keywords:
γ-crystallins, aggregation inhibitors, molecular dockingAbstract
Cataract, the leading cause of blindness worldwide, is characterized by the presence of a cloudy area in the eye lens resulting in a loss of transparency. A number of mechanisms contribute to the longevity and transparency of the human lens, a reducing and oxygen deficient environment, the presence of UV-filters, and most importantly a unique supramolecular organization of its structural proteins, the α-, β- and γ-crystallins. With advancing age, progressively, or due to some mutations, this fragile equilibrium can be perturbed, causing γ-crystallin insolubilization, misfolding, fragmentation and aggregation. In this study, we performed a comparative molecular docking analysis of several experimentally investigated molecules of natural origin, that might protect γ-crystallins from destabilization and aggregation. Our specific protein targets are wild-type human γD-crystallin, and its mutant P23T γD-crystallin, associated with congenital cataract. Thirteen phytochemicals were investigated as potential inhibitors of γD-crystallin aggregation, and we compared their binding energies with those of lanosterol, an ingredient present in over-the-counter eye products, to prevent cataracts. We performed a detailed comparative molecular docking analysis and we found that the binding energies of lanosterol outcompete those of all the other investigated potential natural inhibitors.
References
G.J. Wistow, J. Piatigorsky, Annu. Rev. Biochem., 1988, 57, 479-504.
H. Bloemendal, W. de Jong, R. Jaenicke, N.H. Lubsen, C. Slingsby, A. Tardieu, Progress in Biophysics and Molecular Biology, 2004, 86(3), 407-485.
W.W. Dejong, J.A.M. Leunissen, C.E.M. Voorter, Mol. Biol. Evol., 1993, 10(1), 103-126.
J. Horwitz, Exp. Eye Res., 2009, 88(2), 190-194.
J. Horwitz, M.P. Bova, L.L. Ding, D.A. Haley, P.L. Stewart, Eye, 1999, 13, 403-408.
S. Islam, M.T. Do, B.S. Frank, G.L. Hom, S. Wheeler, H. Fujioka, B. Wang, G. Minocha, D.R. Sell, X. Fan, K.J. Lampi, V.M. Monnier, J. Biol. Chem., 2022, 298(10), 102417.
S. Bassnett, Y.R. Shi, G.F.J.M. Vrensen, Philos. Tans. Roy. Soc. B, 2011, 366(1568), 1250-1264.
N.H. Lubsen, H.J.M. Aarts, J.G.G. Schoenmakers, Prog. Biophys. Mol. Bio., 1988, 51(1), 47-76.
G. Wistow, Molecular Biology and Evolution of Crystallins: Gene Recruitment and Multifunctional Proteins in the Eye Lens, Springer, R.G. Landes Co., Austin, TX., 1995.
M.E. Ray, G. Wistow, Y.A. Su, P.S. Meltzer, J.M. Trent, Prog. Nat. Acad. Sci. USA, 1997, 94(7), 3229-3234.
A. Laganowsky, J.L.P. Benesch, M. Landau, L.L. Ding, M.R. Sawaya, D. Cascio, Q.L. Huang, C.V. Robinson, J. Horwitz, D. Eisenberg, Protein Sci., 2010, 19(5), 1031-1043.
C. Slingsby, G.J. Wistow, A.R. Clark, Protein Sci., 2013, 22(4), 367-380.
J.I. Clark, J.M. Clark, Int. Rev. Cytology, 1999, 192, 171-187.
Z. Kyselova, M. Stefek, V. Bauer, J. Diabetes Complicat., 2004, 18(2), 129-140.
J. Konopinska, M. Mlynarczyk, D.A. Dmuchowska, I. Obuchowska, J. Clin. Med., 2021, 10(13), 2847.
X.J. Fan, V.M. Monnier, J. Whitson, Exp. Eye Res., 2017, 156, 103-111.
A.M. Wood, R.J.W. Truscott, Exp. Eye Res., 1993, 56(3), 317-325.
V.P.R. Vendra, I. Khan, S. Chandani, A. Muniyandi, D. Balasubramanian, Biochim. Biophys. Acta - Gen. Subjects, 2016, 1860(1), 333-343.
M.S. Kosinski-Collins, S.L. Flaugh, J. King, Protein Sci, 2004, 13(8), 2223-2235.
J. Chen, P.R. Callis, J. King, Biochemistry, 2009, 48(17), 3708-3716.
J.C. Boatz, M.J. Whitley, M. Li, A.M. Gronenborn, P.C.A. van der Wel, Nature Commun., 2017, 8(1), 15137.
P. Evans, K. Wyatt, G.J. Wistow, O.A. Bateman, B.A. Wallace, C. Slingsby, J. Mol. Biol., 2004, 343(2), 435-444.
A. Basak, O. Bateman, C. Slingsby, A. Pande, N. Asherie, O. Ogun, G.B. Benedek, J. Pande, J. Mol. Biol., 2003, 328(5), 1137-1147.
A. Pande, O. Annunziata, N. Asherie, O. Ogun, G.B. Benedek, J. Pande, Biochemistry, 2005, 44(7), 2491-2500.
M. Plazanet, C. Floare, M.R. Johnson, R. Schweins, H.P. Trommsdorff, J. Chem. Phys., 2004, 121(11), 5031-5034.
B.J. Bender, S. Gahbauer, A. Luttens, J.K. Lyu, C.M. Webb, R.M. Stein, E.A. Fink, T.E. Balius, J. Carlsson, J.J. Irwin, B.K. Shoichet, Nat. Protoc., 2021, 16(10), 4799-4832.
S. Aci-Sèche, S. Bourg, P. Bonnet, J. Rebehmed, A.G. de Brevern, J. Diharce, Data Brief, 2023, 49, 109386.
M.W. Huff, D.E. Telford, Trends in Pharmacological Sciences, 2005, 26(7), 335-340.
L. Zhao, X.-J. Chen, J. Zhu, Y.-B. Xi, X. Yang, L.-D. Hu, H. Ouyang, S.H. Patel, X. Jin, D. Lin, F. Wu, K. Flagg, H. Cai, G. Li, G. Cao, Y. Lin, D. Chen, C. Wen, C. Chung, Y. Wang, A. Qiu, E. Yeh, W. Wang, X. Hu, S. Grob, R. Abagyan, Z. Su, H.C. Tjondro, X.-J. Zhao, H. Luo, R. Hou, J. Jefferson, P. Perry, W. Gao, I. Kozak, D. Granet, Y. Li, X. Sun, J. Wang, L. Zhang, Y. Liu, Y.-B. Yan, K. Zhang, Nature, 2015, 523(7562), 607-611.
X. Shen, M. Zhu, L. Kang, Y. Tu, L. Li, R. Zhang, B. Qin, M. Yang, H. Guan, J. Ophthalmol., 2018, 2018, 1-9.
K. Wang, M. Hoshino, K. Uesugi, N. Yagi, B.K. Pierscionek, U.P. Andley, Investigative Opthalmol. & Visual Sci., 2022, 63(5), 15.
D.M. Daszynski, P. Santhoshkumar, A.S. Phadte, K.K. Sharma, H.A. Zhong, M.F. Lou, P.F. Kador, Sci. Rep., 2019, 9(1).
Heliostatix Biotechnology, 2023. https://Heliostatix.org. (accessed 1st November 2023 2023).
J. Irwin, Abstr. of Papers of Am. Chem. Soc., 2017, 253.
J.J. Irwin, K.G. Tang, J. Young, C. Dandarchuluun, B.R. Wong, M. Khurelbaatar, Y.S. Moroz, J. Mayfield, R.A. Sayle, J. Chem. Inf. Model., 2020, 60(12), 6065-6073.
M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, G. A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A. V. Marenich, J. Bloino, B. G. Janesko, R. Gomperts, B. Mennucci, H. P. Hratchian, J. V. Ortiz, A. F. Izmaylov, J. L. Sonnenberg, D. Williams-Young, F. Ding, F. Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson,
D. Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell, J. J. A. Montgomery,
J. E. Peralta, F. Ogliaro, M. J. Bearpark, J. J. Heyd, E. N. Brothers, K. N. Kudin, V. N. Staroverov, T. A. Keith, R. Kobayashi, J. Normand, K. Raghavachari,
A. P. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, J. M. Millam,
M. Klene, C. Adamo, R. Cammi, W. Ochterski, R. L. Martin, K. Morokuma,
O. Farkas, J. B. Foresman, D.J. Fox, Gaussian 16, Revision C.02, Gaussian Inc., Wallingford CT: 2016.
A. Basak, O. Bateman, C. Slingsby, A. Pande, N. Asherie, O. Ogun, G.B. Benedek, J. Pande, J. Mol. Biol., 2003, 328(5), 1137-1147.
J. Jung, I.-J.L. Byeon, Y. Wang, J. King, A.M. Gronenborn, Biochemistry, 2009, 48(12), 2597-2609.
G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell, A.J. Olson, J. Comput. Chem., 2009, 30(16), 2785-2791.
O. Trott, A.J. Olson, J. Comput. Chem., 2009, 31(2), 455–461.
H.S. Kang, Z.X. Yang, R.H. Zhou, J. Am. Chem. Soc., 2018, 140(27), 8479-8486.
F. Olawale, O. Iwaloye, I.M. Folorunso, S. Shityakov, J. Comput. Biophys. and Chem., 2022, 22(01), 11-30.
D. Tewari, O. Samoila, D. Gocan, A. Mocan, C. Moldovan, H.P. Devkota, A.G. Atanasov, G. Zengin, J. Echeverria, D. Vodnar, B. Szabo, G. Crisan, Front. in Pharmacology, 2019, 10.
I. Sher-Rosenthal, E. Bubis, Z. Goldberg, M. Samara, A. Elmann, Y. Rotenstreich, Invest. Ophth. Vis. Sci., 2021, 62(8).
A.K. Ghosh, R. Thapa, H.N. Hariani, M. Volyanyuk, S.D. Ogle, K.A. Orloff, S. Ankireddy, K.R. Lai, A. Ziniauskaite, E.B. Stubbs, G. Kalesnykas, J.J. Hakkarainen, K.A. Langert, S. Kaja, Pharmaceutics, 2021, 13(9).
S. Davinelli, S. Ali, G. Scapagnini, C. Costagliola, Front. Nutr., 2021, 8.
H. Matsuda, T. Wang, H. Managi, M. Yoshikawa, Bioorgan. Med. Chem., 2003, 11(24), 5317-5323.
H. Matsuda, T. Morikawa, I. Toguchida, M. Yoshikawa, Chem. Pharm. Bull., 2002, 50(6), 788-795.
B.S. Patil, G.K. Jayaprakasha, K.N.C. Murthy, A. Vikram, J. Agr. Food. Chem., 2009, 57(18), 8142-8160.
S. Majumdar, R. Srirangam, J. Pharm. Pharmacol., 2010, 62(8), 951-965.
W. Kalt, A. Hanneken, P. Milbury, F. Tremblay, J. Agr. Food Chem., 2010, 58(7), 4001-4007.
M. Stefek, Interdiscipl. Toxicol., 2011, 4(2), 69-77.
J.K. Song, D.D. Guo, H.S. Bi, Int. J. Mol. Med., 2018, 41(2), 765-772.
B.P. Mohanty, T. Mitra, S. Ganguly, S. Das Sarkar, A. Mahanty, Biol. Trace Elem. Res., 2021, 199(9), 3354-3359.
J.I. Choi, J. Kim, S.Y. Choung, Mol. Vis., 2019, 25, 118-128.
J. Cao, T. Wang, M. Wang, BMC Ophthalmol., 2018, 18, 48.
X.F. Liu, J.L. Hao, T. Xie, N.J. Mukhtar, W. Zhang, T.H. Malik, C.W. Lu, D.D. Zhou, Front. in Pharmacol., 2017, 8, 66.
J.H. Liao, Y.S. Huang, Y.C. Lin, F.Y. Huang, S.H. Wu, T.H. Wu, J. Agr. Food Chem., 2016, 64(10), 2080-2086.
C.G. Wang, L. Xu, F. Cheng, H.Q. Wang, L.Y. Jia, RSC Adv., 2015, 5(38), 30197-30205.
C.N. Grama, P. Suryanarayana, M.A. Patil, G. Raghu, N. Balakrishna, M.N.V.R. Kumar, G.B. Reddy, Plos One, 2013, 8(10), 78217.
J.W.R. Wu, C.Y. Kao, L.T.W. Lin, W.S. Wen, J.T. Lai, S.S.S. Wang, Biochem. Eng. J., 2013, 78, 189-197.
A. Dawn, V. Goswami, S. Sapra, S. Deep, Langmuir, 2023, 39(3), 1330-1344.
H. Nagashima, N. Sasaki, S. Amano, S. Nakamura, M. Hayano, K. Tsubota, Sci. Rep., 2021, 11(1), 2174.
B. Neha, R. Jannavi, P. Sukumaran, J. Pharm. Res. Int., 2021, 33(29a), 17-32.
J. Jeevanandam, R. Madhumitha, N.T. Saraswathi, J. Mol. Struct., 2021, 1226, 129428.
M. Sakthivel, P. Geraldine, P.A. Thomas, Graef Arch. Clin. Exp. Ophtalmol., 2011, 249(8), 1201-1210.
M.L. Broide, C.R. Berland, J. Pande, O.O. Ogun, G.B. Benedek, Proc. Natl. Acad. Sci. USA, 1991, 88(13), 5660-5664.
E. Matei, A. Zheng, W. Furey, J. Rose, C. Aiken, A.M. Gronenborn, J. Biol. Chem., 2010, 285(17), 13057-13065.
P.A. Ravindranath, S. Forli, D.S. Goodsell, A.J. Olson, M.F. Sanner, Plos Comput. Biol., 2015, 11(12), e1004586.
S. Forli, A.J. Olson, J. Med. Chem., 2012, 55(2), 623-638.
L. El Khoury, D. Santos-Martins, S. Sasmal, J. Eberhardt, G. Bianco, F.A. Ambrosio, L. Solis-Vasquez, A. Koch, S. Forli, D.L. Mobley, J. Comput. Aid. Mol. Des., 2019, 33(12), 1011-1020.
X.B. He, S.H. Liu, T.S. Lee, B.H. Ji, V.H. Man, D.M. York, J.M. Wang, ACS Omega, 2020, 5(9), 4611-4619.
D. Santos-Martins, L. Solis-Vasquez, A.F. Tillack, M.F. Sanner, A. Koch, S. Forli, J. Chem. Theor. Comput., 2021, 17(2), 1060-1073.
S. Brudar, B. Hribar-Lee, J. Mol. Liq., 2023, 386, 122461.
P. Das, J.A. King, R.H. Zhou, Proc. Natl. Acad. Sci. USA, 2011, 108(26), 10514-10519.
J. Gasteiger, M. Marsili, Tetrahedron, 1980, 36(22), 3219-3228.
G.M. Morris, D.S. Goodsell, R.S. Halliday, R. Huey, W.E. Hart, R.K. Belew, A.J. Olson, J. Comput. Chem., 1998, 19(14), 1639-1662.
J. Fuhrmann, A. Rurainski, H.P. Lenhof, D. Neumann, J. Comput. Chem., 2010, 31(9), 1911-1918.
C.G. Floare, M. Bogdan, M. Tomoaia-Cotisel, A. Mocanu, J. Mol. Struct., 2022, 1248, 131477.
M. Mic, A. Pîrnau, C.G. Floare, M. Bogdan, Int. J. Biol. Macromol., 2020, 147, 326-332.
M. Mic, A. Pîrnau, C.G. Floare, G. Marc, A.H. Franchini, O. Oniga, L. Vlase,
M. Bogdan, J. Mol. Struct., 2021, 1244, 131278.
E.F. Pettersen, T.D. Goddard, C.C. Huang, G.S. Couch, D.M. Greenblatt, E.C. Meng, T.E. Ferrin, J. Comput. Chem., 2004, 25(13), 1605-1612.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Studia Universitatis Babeș-Bolyai Chemia

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.