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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Imidazole and Biphenyl Derivatives as Anti-cancer Agents for Glioma Therapeutics: Computational Drug Repurposing Strategy

Author(s): Poornimaa Murali and Ramanathan Karuppasamy*

Volume 23, Issue 9, 2023

Published on: 16 February, 2023

Page: [1085 - 1101] Pages: 17

DOI: 10.2174/1871520623666230125090815

Price: $65


Background: Targeting mutated isocitrate dehydrogenase 1 (mIDH1) is one of the key therapeutic strategies for the treatment of glioma. Few inhibitors, such as ivosidenib and vorasidenib, have been identified as selective inhibitors of mIDH1. However, dose-dependent toxicity and limited brain penetration of the blood-brain barrier remain the major limitations of the treatment procedures using these inhibitors.

Objective: In the present study, computational drug repurposing strategies were employed to identify potent mIDH1- specific inhibitors from the 11,808 small molecules listed in the DrugBank repository.

Methods: Tanimoto coefficient (Tc) calculations were initially used to retrieve compounds with structurally similar scaffolds to ivosidenib. The resultant compounds were then subjected to molecular docking to discriminate the binders from the non-binders. The binding affinities and pharmacokinetic properties of the screened compounds were examined using prime Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) and QikProp algorithm, respectively. The conformational stability of these molecules was validated using 100 ns molecular dynamics simulation.

Results: Together, these processes led to the identification of three-hit molecules, namely DB12001, DB08026, and DB03346, as potential inhibitors of the mIDH1 protein. Of note, the binding free energy calculations and MD simulation studies emphasized the greater binding affinity and structural stability of the hit compounds towards the mIDH1 protein.

Conclusion: The collective evidence from our study indicates the activity of DB12001 against recurrent glioblastoma, which, in turn, highlights the accuracy of our adapted strategy. Hence, we hypothesize that the identified lead molecules could be translated for the development of mIDH1 inhibitors in the near future.

Keywords: Mutated IDH1 protein, tanimoto coefficient, glide docking, prime MM-GBSA, molecular dynamics simulation, glioma.

Graphical Abstract
Lee, J.H.; Lee, J.E.; Kahng, J.Y.; Kim, S.H.; Park, J.S.; Yoon, S.J.; Um, J.Y.; Kim, W.K.; Lee, J.K.; Park, J.; Kim, E.H.; Lee, J.H.; Lee, J.H.; Chung, W.S.; Ju, Y.S.; Park, S.H.; Chang, J.H.; Kang, S.G.; Lee, J.H. Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature, 2018, 560(7717), 243-247.
[] [PMID: 30069053]
Weller, M.; van den Bent, M.; Preusser, M.; Le Rhun, E.; Tonn, J.C.; Minniti, G.; Bendszus, M.; Balana, C.; Chinot, O.; Dirven, L.; French, P.; Hegi, M.E.; Jakola, A.S.; Platten, M.; Roth, P.; Rudà, R.; Short, S.; Smits, M.; Taphoorn, M.J.B.; von Deimling, A.; Westphal, M.; Soffietti, R.; Reifenberger, G.; Wick, W. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat. Rev. Clin. Oncol., 2021, 18(3), 170-186.
[] [PMID: 33293629]
Reifenberger, G.; Wirsching, H.G.; Knobbe-Thomsen, C.B.; Weller, M. Advances in the molecular genetics of gliomas — implications for classification and therapy. Nat. Rev. Clin. Oncol., 2017, 14(7), 434-452.
[] [PMID: 28031556]
Kalidindi, N.; Or, R.; Babak, S.; Mason, W. Molecular classification of diffuse gliomas. Can. J. Neurol. Sci., 2020, 47(4), 464-473.
[] [PMID: 31918786]
Yan, H.; Parsons, D.W.; Jin, G.; McLendon, R.; Rasheed, B.A.; Yuan, W.; Kos, I.; Batinic-Haberle, I.; Jones, S.; Riggins, G.J.; Friedman, H.; Friedman, A.; Reardon, D.; Herndon, J.; Kinzler, K.W.; Velculescu, V.E.; Vogelstein, B.; Bigner, D.D. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med., 2009, 360(8), 765-773.
[] [PMID: 19228619]
Mellai, M.; Caldera, V.; Annovazzi, L.; Schiffer, D. The distribution and significance of IDH mutations in gliomas. In: Evolution of the Molecular Biology of Brain Tumors and Therapeutic Implications; Intechopen: London, 2013; pp. 299-342.
Wang, Y.; Tang, S.; Lai, H.; Jin, R.; Long, X.; Li, N.; Tang, Y.; Guo, H.; Yao, X.; Leung, E.L.H. Discovery of novel IDH1 inhibitor through comparative structure-based virtual screening. Front. Pharmacol., 2020, 11, 579768.
[] [PMID: 33262701]
Suzuki, H.; Aoki, K.; Chiba, K.; Sato, Y.; Shiozawa, Y.; Shiraishi, Y.; Shimamura, T.; Niida, A.; Motomura, K.; Ohka, F.; Yamamoto, T.; Tanahashi, K.; Ranjit, M.; Wakabayashi, T.; Yoshizato, T.; Kataoka, K.; Yoshida, K.; Nagata, Y.; Sato-Otsubo, A.; Tanaka, H.; Sanada, M.; Kondo, Y.; Nakamura, H.; Mizoguchi, M.; Abe, T.; Muragaki, Y.; Watanabe, R.; Ito, I.; Miyano, S.; Natsume, A.; Ogawa, S. Mutational landscape and clonal architecture in grade II and III gliomas. Nat. Genet., 2015, 47(5), 458-468.
[] [PMID: 25848751]
Lu, V.M.; McDonald, K.L. Isocitrate dehydrogenase 1 mutation subtypes at site 132 and their translational potential in glioma. CNS Oncol., 2018, 7(1), 41-50.
[] [PMID: 29303363]
Li, N.; Wang, F.; Niu, S.; Cao, J.; Wu, K.; Li, Y.; Yin, N.; Zhang, X.; Zhu, W.; Yin, Y. Discovery of novel inhibitors of Streptococcus pneumoniae based on the virtual screening with the homology-modeled structure of histidine kinase (VicK). BMC Microbiol., 2009, 9(1), 129.
[] [PMID: 19558698]
Lu, I.L.; Huang, C.F.; Peng, Y.H.; Lin, Y.T.; Hsieh, H.P.; Chen, C.T.; Lien, T.W.; Lee, H.J.; Mahindroo, N.; Prakash, E.; Yueh, A.; Chen, H.Y.; Goparaju, C.M.V.; Chen, X.; Liao, C.C.; Chao, Y.S.; Hsu, J.T.A.; Wu, S.Y. Structure-based drug design of a novel family of PPARgamma partial agonists: Virtual screening, X-ray crystallography, and in vitro/in vivo biological activities. J. Med. Chem., 2006, 49(9), 2703-2712.
[] [PMID: 16640330]
Budzik, B.; Garzya, V.; Shi, D.; Walker, G.; Woolley-Roberts, M.; Pardoe, J.; Lucas, A.; Tehan, B.; Rivero, R.A.; Langmead, C.J.; Watson, J.; Wu, Z.; Forbes, I.T.; Jin, J. Novel N-substituted benzimidazolones as potent, selective, cns-penetrant, and orally active m1 machr agonists. ACS Med. Chem. Lett., 2010, 1(6), 244-248.
[] [PMID: 24900202]
Becker, O.M.; Dhanoa, D.S.; Marantz, Y.; Chen, D.; Shacham, S.; Cheruku, S.; Heifetz, A.; Mohanty, P.; Fichman, M.; Sharadendu, A.; Nudelman, R.; Kauffman, M.; Noiman, S. An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression. J. Med. Chem., 2006, 49(11), 3116-3135.
[] [PMID: 16722631]
Balfour, J.A.; Wilde, M.I. Dorzolamide. Drugs Aging, 1997, 10(5), 384-403.
[] [PMID: 9143858]
Vijayakrishnan, R. Structure-based drug design and modern medicine. J. Postgrad. Med., 2009, 55(4), 301-304.
[] [PMID: 20083886]
Eagling, V.A.; Back, D.J.; Barry, M.G. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br. J. Clin. Pharmacol., 1997, 44(2), 190-194.
[] [PMID: 9278209]
Van Drie, J.H. Computer-aided drug design: The next 20 years. J. Comput. Aided Mol. Des., 2007, 21(10-11), 591-601.
[] [PMID: 17989929]
Liu, K.; Pu, J.; Nie, Z.; Shi, Y.; Jiang, L.; Wu, Q.; Chen, Y.; Yang, C. Ivacaftor inhibits glioblastoma stem cell maintenance and tumor progression. Front. Cell Dev. Biol., 2021, 9, 678209.
[] [PMID: 34046412]
Liu, K.; Jiang, L.; Shi, Y.; Liu, B.; He, Y.; Shen, Q.; Jiang, X.; Nie, Z.; Pu, J.; Yang, C.; Chen, Y. Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. Cell Death Differ., 2022, 29(9), 1834-1849.
[] [PMID: 35301431]
Rohle, D.; Popovici-Muller, J.; Palaskas, N.; Turcan, S.; Grommes, C.; Campos, C.; Tsoi, J.; Clark, O.; Oldrini, B.; Komisopoulou, E.; Kunii, K.; Pedraza, A.; Schalm, S.; Silverman, L.; Miller, A.; Wang, F.; Yang, H.; Chen, Y.; Kernytsky, A.; Rosenblum, M.K.; Liu, W.; Biller, S.A.; Su, S.M.; Brennan, C.W.; Chan, T.A.; Graeber, T.G.; Yen, K.E.; Mellinghoff, I.K. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science, 2013, 340(6132), 626-630.
[] [PMID: 23558169]
Davis, M.I.; Gross, S.; Shen, M.; Straley, K.S.; Pragani, R.; Lea, W.A.; Popovici-Muller, J.; DeLaBarre, B.; Artin, E.; Thorne, N.; Auld, D.S.; Li, Z.; Dang, L.; Boxer, M.B.; Simeonov, A. Biochemical, cellular, and biophysical characterization of a potent inhibitor of mutant isocitrate dehydrogenase IDH1. J. Biol. Chem., 2014, 289(20), 13717-13725.
[] [PMID: 24668804]
Dhillon, S. Ivosidenib: First global approval. Drugs, 2018, 78(14), 1509-1516.
[] [PMID: 30209701]
Konteatis, Z.; Artin, E.; Nicolay, B.; Straley, K.; Padyana, A.K.; Jin, L.; Chen, Y.; Narayaraswamy, R.; Tong, S.; Wang, F.; Zhou, D.; Cui, D.; Cai, Z.; Luo, Z.; Fang, C.; Tang, H.; Lv, X.; Nagaraja, R.; Yang, H.; Su, S.S.M.; Sui, Z.; Dang, L.; Yen, K.; Popovici-Muller, J.; Codega, P.; Campos, C.; Mellinghoff, I.K.; Biller, S.A. Vorasidenib (AG-881): A first-in-class, brain-penetrant dual inhibitor of mutant IDH1 and 2 for treatment of glioma. ACS Med. Chem. Lett., 2020, 11(2), 101-107.
[] [PMID: 32071674]
Caravella, J.A.; Lin, J.; Diebold, R.B.; Campbell, A.M.; Ericsson, A.; Gustafson, G.; Wang, Z.; Castro, J.; Clarke, A.; Gotur, D.; Josephine, H.R.; Katz, M.; Kershaw, M.; Yao, L.; Toms, A.V.; Barr, K.J.; Dinsmore, C.J.; Walker, D.; Ashwell, S.; Lu, W. Structure-based design and identification of FT-2102 (Olutasidenib), a potent mutant-selective IDH1 inhibitor. J. Med. Chem., 2020, 63(4), 1612-1623.
[] [PMID: 31971798]
Zou, F.; Pusch, S.; Eisel, J.; Ma, T.; Zhu, Q.; Deng, D.; Gu, Y.; Xu, Y.; von Deimling, A.; Zha, X. Identification of a novel selective inhibitor of mutant isocitrate dehydrogenase 1 at allosteric site by docking-based virtual screening. RSC Advances, 2016, 6(99), 96735-96742.
Zou, F.; Pusch, S.; Hua, J.; Ma, T.; Yang, L.; Zhu, Q.; Xu, Y.; Gu, Y.; von Deimling, A.; Zha, X. Identification of novel allosteric inhibitors of mutant isocitrate dehydrogenase 1 by cross docking-based virtual screening. Bioorg. Med. Chem. Lett., 2018, 28(3), 388-393.
[] [PMID: 29290542]
Zheng, M.; Sun, W.; Gao, S.; Luan, S.; Li, D.; Chen, R.; Zhang, Q.; Chen, L.; Huang, J.; Li, H. Structure based discovery of clomifene as a potent inhibitor of cancer-associated mutant IDH1. Oncotarget, 2017, 8(27), 44255-44265.
[] [PMID: 28498812]
Duan, Z.; Liu, J.; Niu, L.; Wang, J.; Feng, M.; Chen, H.; Luo, C. Discovery of DC_H31 as potential mutant IDH1 inhibitor through NADPH-based high throughput screening. Bioorg. Med. Chem., 2019, 27(15), 3229-3236.
[] [PMID: 31208797]
Madhavi Sastry, G.; Adzhigirey, M.; Day, T.; Annabhimoju, R.; Sherman, W. Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. J. Comput. Aided Mol. Des., 2013, 27(3), 221-234.
[] [PMID: 23579614]
Liu, R.; AbdulHameed, M.D.M.; Wallqvist, A. Teaching an old dog new tricks: Strategies that improve early recognition in similarity-based virtual screening. Front Chem., 2019, 7, 701.
[] [PMID: 31709231]
Capecchi, A.; Probst, D.; Reymond, J.L. One molecular fingerprint to rule them all: Drugs, biomolecules, and the metabolome. J. Cheminform., 2020, 12(1), 43.
[] [PMID: 33431010]
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(7), 1739-1749.
[] [PMID: 15027865]
Poonan, P.; Agoni, C.; Soliman, M.E.S. Dual‐knockout of mutant isocitrate dehydrogenase 1 and 2 subtypes towards glioma therapy: Structural mechanistic insights on the role of vorasidenib. Chem. Biodivers., 2021, 18(7), e2100110.
[] [PMID: 33982420]
Repasky, M.P.; Shelley, M.; Friesner, R.A. Flexible ligand docking with glide. Curr. Protoc. Bioinformatics, 2007, 8(1), 12.
[PMID: 18428795]
Lyne, P.D.; Lamb, M.L.; Saeh, J.C. Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. J. Med. Chem., 2006, 49(16), 4805-4808.
[] [PMID: 16884290]
Wang, Y.; Xing, J.; Xu, Y.; Zhou, N.; Peng, J.; Xiong, Z.; Liu, X.; Luo, X.; Luo, C.; Chen, K.; Zheng, M.; Jiang, H. In silico ADME/T modelling for rational drug design. Q. Rev. Biophys., 2015, 48(4), 488-515.
[] [PMID: 26328949]
Leeson, P.D.; Young, R.J. Molecular property design: Does everyone get it. ACS Med. Chem. Lett., 2015, 6(7), 722-725.
[] [PMID: 26191353]
Banerjee, P.; Eckert, A.O.; Schrey, A.K.; Preissner, R. ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res., 2018, 46(W1), W257-W263.
[] [PMID: 29718510]
Lagunin, A.; Stepanchikova, A.; Filimonov, D.; Poroikov, V. PASS: Prediction of activity spectra for biologically active substances. Bioinformatics, 2000, 16(8), 747-748.
[] [PMID: 11099264]
Alamri, M.A. Pharmacoinformatics and molecular dynamic simulation studies to identify potential small-molecule inhibitors of WNK-SPAK/OSR1 signaling that mimic the RFQV motifs of WNK kinases. Arab. J. Chem., 2020, 13(4), 5107-5117.
Wang, H.; Dommert, F.; Holm, C. Optimizing working parameters of the smooth particle mesh Ewald algorithm in terms of accuracy and efficiency. J. Chem. Phys., 2010, 133(3), 034117.
[] [PMID: 20649318]
Amiri, S.; Sansom, M.S.P.; Biggin, P.C. Molecular dynamics studies of AChBP with nicotine and carbamylcholine: The role of water in the binding pocket. Protein Eng. Des. Sel., 2007, 20(7), 353-359.
[] [PMID: 17595341]
Kumar, A.; Rajendran, V.; Sethumadhavan, R.; Purohit, R. Molecular dynamic simulation reveals damaging impact of RAC1 F28L mutation in the switch I region. PLoS One, 2013, 8(10), e77453.
[] [PMID: 24146998]
Ripphausen, P.; Nisius, B.; Bajorath, J. State-of-the-art in ligand-based virtual screening. Drug Discov, 2011, 16(9-10), 372-376.
[PMID: 21349346]
Friesner, R.A.; Murphy, R.B.; Repasky, M.P.; Frye, L.L.; Greenwood, J.R.; Halgren, T.A.; Sanschagrin, P.C.; Mainz, D.T. Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem., 2006, 49(21), 6177-6196.
[] [PMID: 17034125]
Massova, I.; Kollman, P.A. Combined molecular mechanical and continuum solvent approach (MM-PBSA/GBSA) to predict ligand binding. Perspect. Drug Discov. Des., 2000, 18(1), 113-135.
Genheden, S.; Ryde, U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin. Drug Discov., 2015, 10(5), 449-461.
[] [PMID: 25835573]
Li, J.; Zhou, N.; Luo, K.; Zhang, W.; Li, X.; Wu, C.; Bao, J. In silico discovery of potential VEGFR-2 inhibitors from natural derivatives for anti-angiogenesis therapy. Int. J. Mol. Sci., 2014, 15(9), 15994-16011.
[] [PMID: 25216334]
Golub, D.; Iyengar, N.; Dogra, S.; Wong, T.; Bready, D.; Tang, K.; Modrek, A.S.; Placantonakis, D.G. Mutant isocitrate dehydrogenase inhibitors as targeted cancer therapeutics. Front. Oncol., 2019, 9, 417.
[] [PMID: 31165048]
Karthick, V.; Ramanathan, K. Computational investigation of oseltamivir resistance in influenza A (H5N1) virus. Med. Chem. Res., 2013, 22(12), 5764-5771.
Patnaik, A.; Rosen, L.S.; Tolaney, S.M.; Tolcher, A.W.; Goldman, J.W.; Gandhi, L.; Papadopoulos, K.P.; Beeram, M.; Rasco, D.W.; Hilton, J.F.; Nasir, A.; Beckmann, R.P.; Schade, A.E.; Fulford, A.D.; Nguyen, T.S.; Martinez, R.; Kulanthaivel, P.; Li, L.Q.; Frenzel, M.; Cronier, D.M.; Chan, E.M.; Flaherty, K.T.; Wen, P.Y.; Shapiro, G.I. Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors. Cancer Discov., 2016, 6(7), 740-753.
[] [PMID: 27217383]
Tate, S.C.; Sykes, A.K.; Kulanthaivel, P.; Chan, E.M.; Turner, P.K.; Cronier, D.M. A population pharmacokinetic and pharmacodynamic analysis of abemaciclib in a phase I clinical trial in cancer patients. Clin. Pharmacokinet., 2018, 57(3), 335-344.
[] [PMID: 28540640]
Wender, I.O.; Haines, K.; Jahanzeb, M. Response to abemaciclib after 10 lines of therapy including palbociclib in metastatic breast cancer: A case report with literature review. Oncol. Ther., 2020, 8(2), 351-358.
[] [PMID: 32876928]
Kamal, A.; Bharath, K.G.; Lakshma, N.V.; Reddy, V.S.; Shaik, A.B.; Rajender, R.; Kashi, R.M. Design, synthesis and biological evaluation of imidazopyridine/imidazopyrimidine-benzimidazole conjugates as potential anticancer agents. MedChemComm, 2015, 6(4), 606-612.
Mohit, A.A.; Martin, J.H.; Miller, C.A. p493F12 kinase: A novel MAP kinase expressed in a subset of neurons in the human nervous system. Neuron, 1995, 14(1), 67-78.
[] [PMID: 7826642]
Purkey, H.E.; Palaninathan, S.K.; Kent, K.C.; Smith, C.; Safe, S.H.; Sacchettini, J.C.; Kelly, J.W. Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: Rationalizing rodent PCB toxicity. Chem. Biol., 2004, 11(12), 1719-1728.
[] [PMID: 15610856]
Ferreira, L.M.; Azambuja, J.H.; da Silveira, E.F.; Marcondes, S.M.H.; da Cruz, W.F.B.; Costa, P.V.; Gelsleichter, N.E.; Beckenkamp, L.R.; da Cruz, F.M.; Spanevello, R.M.; Wink, M.R.; de Cassia, S.A.A.; Nogueira, C.W.; Braganhol, E.; Cruz, L. Antitumor action of diphenyl diselenide nanocapsules: In vitro assessments and preclinical evidence in an animal model of glioblastoma multiforme. J. Trace Elem. Med. Biol., 2019, 55, 180-189.
[] [PMID: 31345356]
Wade, R.C.; Goodford, P.J. The role of hydrogen-bonds in drug binding. Prog. Clin. Biol. Res., 1989, 289, 433-444.
[PMID: 2726808]
Patil, R.; Das, S.; Stanley, A.; Yadav, L.; Sudhakar, A.; Varma, A.K. Optimized hydrophobic interactions and hydrogen bonding at the target-ligand interface leads the pathways of drug-designing. PLoS One, 2010, 5(8), e12029.
[] [PMID: 20808434]
Hughes, J.P.; Rees, S.; Kalindjian, S.B.; Philpott, K.L. Principles of early drug discovery. Br. J. Pharmacol., 2011, 162(6), 1239-1249.
[] [PMID: 21091654]
Reynolds, C.H.; Reynolds, R.C. Group additivity in ligand binding affinity: An alternative approach to ligand efficiency. J. Chem. Inf. Model., 2017, 57(12), 3086-3093.
[] [PMID: 29111708]
Al-Jarf, R.; de Sá, A.G.C.; Pires, D.E.V.; Ascher, D.B. pdCSM-cancer: Using graph-based signatures to identify small molecules with anticancer properties. J. Chem. Inf. Model., 2021, 61(7), 3314-3322.
[] [PMID: 34213323]
Ali, S.; Khan, F.; Mohammad, T.; Lan, D.; Hassan, M.; Wang, Y. Identification and evaluation of inhibitors of lipase from Malassezia restricta using virtual high-throughput screening and molecular dynamics studies. Int. J. Mol. Sci., 2019, 20(4), 884.
[] [PMID: 30781686]
Hubbard, R.E.; Kamran, H.M. Hydrogen bonds in proteins: Role and strength. In: Encyclopedia of Life Sciences (ELS); John Wiley & Sons, Ltd: Chichester, 2010; pp. 1-7.
Baig, M.H.; Sudhakar, D.R.; Kalaiarasan, P.; Subbarao, N.; Wadhawa, G.; Lohani, M.; Khan, M.K.A.; Khan, A.U. Insight into the effect of inhibitor resistant S130G mutant on physico-chemical properties of SHV type beta-lactamase: A molecular dynamics study. PLoS One, 2014, 9(12), e112456.
[] [PMID: 25479359]
Shukla, R.; Singh, T.R. Virtual screening, pharmacokinetics, molecular dynamics and binding free energy analysis for small natural molecules against cyclin-dependent kinase 5 for Alzheimer’s disease. J. Biomol. Struct. Dyn., 2019, 38(1), 248-262.
[PMID: 30688165]
Wolf, A.; Kirschner, K.N. Principal component and clustering analysis on molecular dynamics data of the ribosomal L11·23S subdomain. J. Mol. Model., 2013, 19(2), 539-549.
[] [PMID: 22961589]
Verma, S.; Grover, S.; Tyagi, C.; Goyal, S.; Jamal, S.; Singh, A.; Grover, A. Hydrophobic interactions are a key to MDM2 inhibition by polyphenols as revealed by molecular dynamics simulations and MM/PBSA free energy calculations. PLoS One, 2016, 11(2), e0149014.
[] [PMID: 26863418]
Tavernelli, I.; Cotesta, S.; Di Iorio, E.E. Protein dynamics, thermal stability, and free-energy landscapes: A molecular dynamics investigation. Biophys. J., 2003, 85(4), 2641-2649.
[] [PMID: 14507727]

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