In silico analysis of plasmodium falciparum CDPK5 protein through molecular modeling, docking and dynamics. (English) Zbl 1406.92209

Summary: Calcium-dependent protein kinase 5 (CDPK5) protein is one of the family members of a calcium-dependent protein kinase that is found in plants and some species of protozoa which includes Plasmodium falciparum (Pf), the pathogen responsible for malaria. CDPKs regulate many biological processes in apicomplexans such as Plasmodium, Toxoplasma or Cryptosporidium. The study addresses the similarity in sequences and evolutionary relationship of CDPK5 across apicomplexans. Further, the three-dimensional structural conformation of PfCDPK5 is generated through homology modeling. Molecular dynamics simulation of the homology model for a time interval of 40 ns resulted in a stable conformation of the PfCDPK5 protein. Inhibitor identification was carried out from computational screening of known anti-malarial compounds. The reliability of the binding mode for the best inhibitor compound MMV687246 was validated through a complex molecular dynamics study. This findings advocates that MMV687246 from Pathogen Box as the best inhibitor against PfCDPK5 protein and can be considered for experimental validation study in future.


92C40 Biochemistry, molecular biology
92D20 Protein sequences, DNA sequences
Full Text: DOI


[1] Aher, R. B.; Roy, K., Exploring structural requirements for the inhibition of Plasmodium falciparum calcium-dependent protein kinase-4 (Pf CDPK-4) using multiple in silico approaches, RSC Adv., 6, 51957-51982, (2016)
[2] Almela, M. J.; Lozano, S.; Lelièvre, J.; Colmenarejo, G.; Coterón, J. M.; Rodrigues, J.; Gonzalez, C.; Herreros, E., A new set of chemical starting points with Plasmodium falciparum transmission-blocking potential for antimalarial drug discovery, PLoS One, 10, (2015)
[3] Altschul, S. F.; Madden, T. L.; Schaffer, A. A.; Zhang, J.; Zhang, Z.; Miller, W.; Lipman, D. J., Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res., 25, 3389-3402, (1997)
[4] Andersen, H. C., Molecular dynamics simulations at constant pressure and/or temperature, J. Chem. Phy., 72, 2384-2393, (1980)
[5] Aurrecoechea, C.; Brestelli, J.; Brunk, B. P.; Dommer, J.; Fischer, S.; Gajria, B.; Heiges, M., PlasmoDB: a functional genomic database for malaria parasites, Nucleic Acids Res., 37, D539-D543, (2008)
[6] Avery, V. M.; Bashyam, S.; Burrows, J. N.; Duffy, S.; Papadatos, G.; Puthukkuti, S.; Willis, P., Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum, Malar. J., 13, 190, (2014)
[7] Bairoch, A.; Apweiler, R.; Wu, C. H.; Barker, W. C.; Boeckmann, B.; Ferro, S.; Gasteiger, E.; Huang, H.; Lopez, R.; Magrane, M.; Martin, M. J., The universal protein resource (UniProt), Nucleic Acids Res., 33, D154-D159, (2005)
[8] Berardi, M. J.; Shih, W. M.; Harrison, S. C.; Chou, J. J., Mitochondrial uncoupling protein 2 structure determined by NMR molecular fragment searching, Nature, 476, 09, (2011)
[9] Berendsen, H. J.; van der Spoel, D.; van Drunen, R., GROMACS: a message-passing parallel molecular dynamics implementation, Comput. Phys. Commun., 91, 43-56, (1995)
[10] Bernstein, F. C.; Koetzle, T. F.; Williams, G. J.; Meyer, E. F.; Brice, M. D.; Rodgers, J. R.; Kennard, O.; Shimanouchi, T.; Tasumi, M., The Protein Data Bank: a computer-based archival file for macromolecular structures, Arch. Biochem. Biophys., 185, 584-591, (1978)
[11] Billker, O.; Lourido, S.; Sibley, L. D., Calcium-dependent signaling and kinases in apicomplexan parasites, Cell Host Microbe, 5, 612-622, (2009)
[12] Birnbaum, J.; Flemming, S.; Reichard, N.; Soares, A. B.; Mesén-Ramírez, P.; Jonscher, E.; Spielmann, T., A genetic system to study Plasmodium falciparum protein function, Nat. Methods, 14, 4, 450, (2017)
[13] Brochet, M.; Billker, O., Calcium signalling in malaria parasites, Mol. Microbio., 100, 397-408, (2016)
[14] Chandran, V.; Stollar, E. J.; Lindorff-Larsen, K.; Harper, J. F.; Chazin, W. J.; Dobson, C. M.; Christodoulou, J., Structure of the regulatory apparatus of a calcium-dependent protein kinase (CDPK): a novel mode of calmodulin-target recognition, J. Mol. Bio., 357, 400-410, (2006)
[15] Chen, W.; Feng, P. M.; Lin, H.; Chou, K. C., iSS-PseDNC: identifying splicing sites using pseudo dinucleotide composition, BioMed Res. Int., 2014, (2014)
[16] Chen, W.; Ding, H.; Feng, P.; Lin, H.; Chou, K. C., iACP: a sequence-based tool for I dentifying anticancer peptides, Oncotarget, 7, 16895, (2016)
[17] Chen, W.; Tang, H.; Ye, J.; Lin, H.; Chou, K. C., iRNA-PseU: Identifying RNA pseudouridine sites, Mol. Ther.-Nucleic Acids, 5, 2016, e332, (2016)
[18] Chen, W.; Feng, P.; Yang, H.; Ding, H.; Lin, H.; Chou, K. C., iRNA-AI: identifying the adenosine to inosine editing sites in RNA sequences, Oncotarget, 8, 4208, (2017)
[19] Cheng, X.; Zhao, S. G.; Xiao, X.; Chou, K. C., iATC-mISF: a multi-label classifier for predicting the classes of anatomical therapeutic chemicals, Bioinformatics, 33, 341-346, (2016)
[20] Cheng, X.; Xiao, X.; Chou, K. C., pLoc-mPlant: predict subcellular localization of multi-location plant proteins by incorporating the optimal GO information into general PseAAC, Mol. Biosyst., 13, 1722-1727, (2017)
[21] Cheng, X.; Zhao, S. G.; Xiao, X.; Chou, K. C., iATC-mHyb: a hybrid multi-label classifier for predicting the classification of anatomical therapeutic chemicals, Oncotarget, 8, 58494, (2017)
[22] Cheng, X.; Xiao, X.; Chou, K. C., pLoc-mHum: predict subcellular localization of multi-location human proteins via general PseAAC to winnow out the crucial GO information, Bioinformatics, 34, 1448-1456, (2017)
[23] Cheng, X.; Xiao, X.; Chou, K. C., pLoc-mEuk: predict subcellular localization of multi- label eukaryotic proteins by extracting the key GO information into general PseAAC, Genomics, 110, 50-58, (2018)
[24] Chou, K. C.; Chen, N. Y.; Forsen, S., The biological functions of low-frequency phonons. 2. Cooperative effects, Chemic. Scr., 18, 126-132, (1981)
[25] Chou, K. C., Low-frequency collective motion in biomacromolecules and its biological functions, Biophys. Chem., 30, 3-48, (1988)
[26] Chou, K. C.; Mao, B., Collective motion in DNA and its role in drug intercalation, Biopolym. Orig. Res. Biomol., 27, 1795-1815, (1988)
[27] Chou, K. C., Low-frequency resonance and cooperativity of hemoglobin, Trends Biochem. Sci., 14, 212, (1989)
[28] Chou, K. C.; Maggiora, G. M.; Mao, B., Quasi-continuum models of twist-like and accordion-like low-frequency motions in DNA, Biophys. J., 56, 295-305, (1989)
[29] Chou, K. C.; Zhang, C. T.; Maggiora, G. M., Solitary wave dynamics as a mechanism for explaining the internal motion during microtubule growth, Biopolym. Orig. Res. Biomol., 34, 143-153, (1994)
[30] Chou, K. C.; Jones, D.; Heinrikson, R. L., Prediction of the tertiary structure and substrate binding site of caspase-8, FEBS Lett., 419, 49-54, (1997)
[31] Chou, K. C.; Watenpaugh, K. D.; Heinrikson, R. L., A model of the complex between cyclin-dependent kinase 5 and the activation domain of neuronal Cdk5 activator, Biochem. Biophys. Res. Commun., 259, 420-428, (1999)
[32] Chou, K. C.; Tomasselli, A. G.; Heinrikson, R. L., Prediction of the tertiary structure of a caspase-9/inhibitor complex, FEBS Lett., 470, 249-256, (2000)
[33] Chou, K. C.; Wei, D. Q.; Zhong, W. Z., Binding mechanism of coronavirus main proteinase with ligands and its implication to drug design against SARS, Biochem. Biophys. Res. Commun., 308, 148-151, (2003)
[34] Chou, K. C., Structural bioinformatics and its impact to biomedical science, Curr. Med. Chem., 11, 2105-2134, (2004)
[35] Chou, K. C., Molecular therapeutic target for type-2 diabetes, J. Proteome Res., 3, 1284-1288, (2004)
[36] Chou, K. C., Coupling interaction between thromboxane A2 receptor and alpha-13 subunit of guanine nucleotide-binding protein, J. Proteome Res., 4, 1681-1686, (2005)
[37] Chou, K. C.; Shen, H. B., Recent advances in developing web-servers for predicting protein attributes, Nat. Sci., 1, 63, (2009)
[38] Chou, K. C., Impacts of bioinformatics to medicinal chemistry, Med. Chem., 11, 218-234, (2015)
[39] Chou, K. C., An unprecedented revolution in medicinal chemistry driven by the progress of biological science, Curr. Top. Med. Chem., 17, 2337-2358, (2017)
[40] Colovos, C.; Yeates, T. O., Verification of protein structures: patterns of nonbonded atomic interactions, Protein Sci., 9, 1511-1519, (1993)
[41] Crowther, G. J.; Hillesland, H. K.; Keyloun, K. R.; Reid, M. C.; Lafuente-Monasterio, M. J.; Ghidelli-Disse, S.; Leonard, S. E.; He, P.; Jones, J. C.; Krahn, M. M.; Mo, J. S., Biochemical screening of five protein kinases from Plasmodium falciparum against 14,000 cell-active compounds, PLoS One, 11, (2016)
[42] Darden, T.; York, D.; Pedersen, L., Particle mesh Ewald: an N-log (N) method for Ewald ums in large systems, J. Chem. Phy., 98, 10089-10092, (1993)
[43] DeLano, W.L., 2002. Pymol: An open-source molecular graphics tool. CCP4 Newsletter on Protein Crystallography 40, 82-92.
[44] Dev, J.; Park, D.; Fu, Q.; Chen, J.; Ha, H. J.; Ghantous, F.; Herrmann, T.; Chang, W.; Liu, Z.; Frey, G.; Seaman, M. S.; Chen, B.; Chou, J. J., Structural basis for membrane anchoring of HIV-1 envelope spike, Science., 172-175, (2016)
[45] Doerig, C.; Meijer, L., Antimalarial drug discovery: targeting protein kinases, Expert Opin. Ther. Targets, 11, 279-290, (2007)
[46] Dvorin, J. D.; Martyn, D. C.; Patel, S. D.; Grimley, J. S.; Collins, C. R.; Hopp, C. S.; Baker, D. A., A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes, Science, 328, 910-912, (2010)
[47] Eisenberg, D.; Luthy, R.; Bowie, J. U., VERIFY3D: Assessment of protein models with three-dimensional profiles, Methods Enzymol., 277, 396-404, (1997)
[48] Efron, B., The jackknife, the bootstrap, and other resampling plans, Soc. Ind. Appl. Math., 38, (1982) · Zbl 0496.62036
[49] Felsenstein, J., Confidence limits on phylogenies: an approach using the bootstrap, Evolution, 39, 783-791, (1985)
[50] Feng, P. M.; Chen, W.; Lin, H.; Chou, K. C., iHSP-PseRAAAC: Identifying the heat shock protein families using pseudo reduced amino acid alphabet composition, Anal. Biochem., 442, 118-125, (2013)
[51] Feng, P.; Ding, H.; Yang, H.; Chen, W.; Lin, H.; Chou, K. C., iRNA-PseColl: identifying the occurrence sites of different RNA modifications by incorporating collective effects of nucleotides into PseKNC, Mol. Ther.-Nucleic Acids, 7, 55-163, (2017)
[52] Fu, Q.; Fu, T. M.; Cruz, A. C.; Sengupta, P.; Thomas, S. K.; Wang, S.; Siegel, R. M.; Wu, H.; Chou, J. J., Structural basis and functional role of intramembrane trimerization of the Fas/CD95 death receptor, Mol. Cell, 61, 602-613, (2016)
[53] Gaulton, A.; Hersey, A.; Nowotka, M.; Bento, A. P.; Chambers, J.; Mendez, D.; Mutowo, P.; Atkinson, F.; Bellis, L. J.; Cibrián-Uhalte, E.; Davies, M., The ChEMBL database in 2017, Nucleic Acids Res., 45, D945-D954, (2016)
[54] Goldgof, G. M.; Durrant, J. D.; Ottilie, S.; Vigil, E.; Allen, K. E.; Gunawan, F.; LaMonte, G. M., Comparative chemical genomics reveals that the spiroindolone antimalarial KAE609 (Cipargamin) is a P-type ATPase inhibitor, Sci. Rep., 6, 27806, (2016)
[55] Gordon, G. A., Designed electromagnetic pulsed therapy: clinical applications, J. Cell. Physiol., 212, 579-582, (2007)
[56] Gordon, G. A., Extrinsic electromagnetic fields, low frequency (phonon) vibrations, and control of cell function: a non-linear resonance system, J. Biomed. Sci. Eng., 1, 52, (2008)
[57] Harper, J. F.; Harmon, A., Plants, symbiosis, and parasites: a calcium signaling connection, Nat. Rev. Mol. Cell Biol., 6, 555-565, (2005)
[58] Hess, B.; Bekker, H.; Berendsen, H. J.; Fraaije, J. G., LINCS: a linear constraint solver for molecular simulations, J. Comput. Chem., 18, 1463-1472, (1997)
[59] Huang, R. B.; Du, Q. S.; Wang, C. H.; Chou, K. C., An in-depth analysis of the biological functional studies based on the NMR M2 channel structure of influenza A virus, Biochem. Biophys. Res. Commun., 377, 1243-1247, (2008)
[60] Hunter, S.; Apweiler, R.; Attwood, T. K.; Bairoch, A.; Bateman, A.; Binns, D.; Bork, P.; Das, U.; Daugherty, L.; Duquenne, L.; Finn, R. D., InterPro: the integrative protein signature database, Nucleic. Acids. Res., 37, D211-D215, (2008)
[61] Irwin, J. J.; Shoichet, B. K.; Mysinger, M. M.; Huang, N.; Colizzi, F.; Wassam, P.; Cao, Y., Automated docking screens: a feasibility study, J. Med. Chem., 52, 5712, (2009)
[62] Irwin, J. J.; Shoichet, B. K., Zinc-free database of commercially available compounds for virtual screening, J. Chem. Inf. Model., 45, 177-182, (2005)
[63] Jia, J.; Liu, Z.; Xiao, X.; Liu, B.; Chou, K. C., pSuc-Lys: predict lysine succinylation s ites in proteins with PseAAC and ensemble random forest approach, J. Theor. Biol., 394, 223-230, (2016) · Zbl 1343.92153
[64] Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J., Development and testing of the OPLS all-atom force field on conformational energetic and properties of organic liquids, J. Am. Chem. Soc., 118, 11225-11236, (1996)
[65] Kadian, K.; Gupta, Y.; Kempaiah, P.; Gupta, N.; Sharma, A.; Rawat, M., Calcium-Dependent Protein Kinases (CDPKs): key to malaria eradication, Curr. Top. Med. Chem., 17, 2215-2220, (2017)
[66] Kelley, L. A.; Mezulis, S.; Yates, C. M.; Wass, M. N.; Sternberg, M. J., The Phyre2 web portal for protein modeling, prediction, and analysis, Nat. Protoc., 10, 845-858, (2015)
[67] Chen, N. Y., The biological functions of low-frequency phonons, Sci. Sin., 20, 447-457, (1977)
[68] Kumar, S.; Stecher, G.; Tamura, K., MEGA7: Molecular Evolutionary Genetics Analysis version 7.0 for bigger datasets, Mol. Bio. and Evol., 33, 1870-1874, (2016)
[69] Li, X. B.; Wang, S. Q.; Xu, W. R.; Wang, R. L.; Chou, K. C., Novel inhibitor design for hemagglutinin against H1N1 influenza virus by core hopping method, PLoS One, 6, 28111, (2011)
[70] Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M., PROCHECK: a program to check the stereochemical quality of protein structures, J. App. Crystal., 26, 283-291, (1993)
[71] Lasonder, E.; Green, J. L.; Grainger, M.; Langsley, G.; Holder, A. A., Extensive differential protein phosphorylation as intraerythrocytic Plasmodium falciparum schizonts develop into extracellular invasive merozoites, Proteomics, 15, 2716-2729, (2015)
[72] Lemkul, J. A.; Allen, W. J.; Bevan, D. R., Practical considerations for building GROMOS- compatible small-molecule topologies, J. Chem. Inf. Mod., 50, 2221-2235, (2010)
[73] Lucantoni, L.; Duffy, S.; Adjalley, S. H.; Fidock, D. A.; Avery, V. M., Identification of MMV malaria box inhibitors of Plasmodium falciparum early-stage gametocytes using a luciferase-based high-throughput assay. Antimicro, Agents and Chemoth, 57, 6050-6062, (2013)
[74] Lucet, I. S.; Tobin, A.; Drewry, D.; Wilks, A. F.; Doerig, C., Plasmodium kinases as targets for new-generation antimalarials, Future Med. Chem., 4, 2295-2310, (2012)
[75] Ma, Y.; Wang, S. Q.; Xu, W. R.; Wang, R. L.; Chou, K. C., Design novel dual agonists for treating type-2 diabetes by targeting peroxisome proliferator-activated receptors with core hopping approach, PLoS One, 7, 38546, (2012)
[76] Martel, P., Biophysical aspects of neutron scattering from vibrational modes of proteins, Prog. Biophys. Mol. Biol., 57, 129-179, (1992)
[77] Madkan, A.; Blank, M.; Elson, E.; Chou, K. C.; Geddis, M. S.; Goodman, R., Steps to the clinic with ELF EMF, Nat. Sci., 1, 157, (2009)
[78] Mbengue, A.; Bhattacharjee, S.; Pandharkar, T.; Liu, H.; Estiu, G.; Stahelin, R. V.; Rizk, S. S.; Njimoh, D. L.; Ryan, Y.; Chotivanich, K.; Nguon, C., A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria, Nature, 520, 683-687, (2015)
[79] Miller, L. H.; Ackerman, H. C.; Su, X. Z.; Wellems, T. E., Malaria biology and disease pathogenesis: insights for new treatments, Nat. Med., 19, 156-167, (2013)
[80] O’Boyle, N. M.; Banck, M.; James, C. A.; Morley, C.; Vandermeersch, T.; Hutchison, G. R., Open babel: an open chemical toolbox, J. Cheminf., 3, 33, (2011)
[81] OuYang, B.; Xie, S.; Berardi, M. J.; Zhao, X.; Dev, J.; Yu, W.; Sun, B.; Chou, J. J., Unusual architecture of the p7 channel from hepatitis C virus, Nature, 498, 521, (2013)
[82] Oxenoid, K.; Dong, Y.; Cao, C.; Cui, T.; Sancak, Y.; Markhard, A. L.; Grabarek, Z.; Kong, L.; Liu, Z.; Ouyang, B.; Cong, Y., Architecture of the mitochondrial calcium uniporter, Nature, 533, 269, (2016)
[83] Pielak, R. M.; Schnell, J. R.; Chou, J. J., Mechanism of drug inhibition and drug resistance of influenza A M2 channel, (Proceedings of the National Academy of Sciences, (2009)), pnas-0902548106
[84] Partridge, F. A.; Brown, A. E.; Buckingham, S. D.; Willis, N. J.; Wynne, G. M.; Forman, R.; Lomas, D. A., An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes, Int. J. Parasitol Drugs Drug Resist., 8, 8-21, (2018)
[85] 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., 25, 1605-1612, (2004)
[86] Qiu, W. R.; Jiang, S. Y.; Xu, Z. C.; Xiao, X.; Chou, K. C., iRNAm5C-PseDNC: identifying RNA 5-methylcytosine sites by incorporating physical-chemical properties into pseudo dinucleotide composition, Oncotarget, 8, 41178, (2017)
[87] Rottmann, M.; McNamara, C.; Yeung, B. K.; Lee, M. C.; Zou, B.; Russell, B.; Cohen, S. B., Spiroindolones, a new and potent chemotype for the treatment of malaria, Science, 329, 1175, (2010)
[88] Roy, A.; Kucukural, A.; Zhang, Y., I-TASSER: a unified platform for automated protein structure and function prediction, Nat. Prot., 5, 725, (2010)
[89] Schnell, J. R.; Chou, J. J., Structure and mechanism of the M2 proton channel of influenza A virus, Nature, 451, 591, (2008)
[90] SchuÈttelkopf, A. W.; Van Aalten, D. M., PRODRG: a tool for high-throughput crystallography of protein-ligand complexes, Acta Crystallo. Section D: Bio. Crystallo., 60, 1355-1363, (2004)
[91] Schultz, J.; Copley, R. R.; Doerks, T.; Ponting, C. P.; Bork, P., SMART: a web-based tool for the study of genetically mobile domains, Nucleic Acids Res, 28, 231-234, (2000)
[92] Schwede, T.; Kopp, J.; Guex, N.; Peitsch, M. C., SWISS-MODEL: an automated protein homology-modeling server, Nucleic Acids Res, 31, 3381-3385, (2003)
[93] Sievers, F.; Wilm, A.; Dineen, D.; Gibson, T. J.; Karplus, K.; Li, W.; Lopez, R.; McWilliam, H.; Remmert, M.; Söding, J.; Thompson, J. D., Fast, scalable generation of high quality protein multiple sequence alignments using clustal omega, Mol. Syst. Biol., 7, 539, (2011)
[94] Sonnhammer, E. L.; Eddy, S. R.; Durbin, R., Pfam: a comprehensive database of protein domain families based on seed alignments, Proteins-Struct. Funct. Genet., 28, 405-420, (1997)
[95] Spangenberg, T.; Burrows, J. N.; Kowalczyk, P.; McDonald, S.; Wells, T. N.; Willis, P., The open access malaria box: a drug discovery catalyst for neglected diseases, PLoS One, 8, e62906, (2013)
[96] Spillman, N. J.; Kirk, K., The malaria parasite cation ATPase PfATP4 and its role in the mechanism of action of a new arsenal of antimalarial drugs, Int. J. Parasitol Drugs Drug Resist., 5, 149-162, (2015)
[97] Tamura, K.; Peterson, D.; Peterson, N.; Stecher, G.; Nei, M.; Kumar, S., MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods, Mol. Bio. and Evol., 28, 2731-2739, (2011)
[98] Trott, O.; Olson, A. J., AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem., 31, 455-461, (2010)
[99] Consortium, UniProt, UniProt: a hub for protein information, Nucleic Acids Res., 43, D204-D212, (2014)
[100] Van Der Spoel, D.; Lindahl, E.; Hess, B.; Groenhof, G.; Mark, A. E.; Berendsen, H. J., GROMACS: fast, flexible, and free, J. Comput. Chem., 26, 1701-1718, (2005)
[101] Vaidya, A. B.; Morrisey, J. M.; Zhang, Z.; Das, S.; Daly, T. M.; Otto, T. D.; Spillman, N. J.; Wyvratt, M.; Siegl, P.; Marfurt, J.; Wirjanata, G.; Sebayang, B. F.; Price, R. N.; Chatterjee, A.; Nagle, A.; Stasiak, M.; Charman, S. A.; Angulo-Barturen, I.; Ferrer, S.; Belen Jimenez-Diaz, M.; Martinez, M. S.; Gamo, F. J.; Avery, V. M.; Ruecker, A.; Delves, M.; Kirk, K.; Berriman, M.; Kortagere, S.; Burrows, J.; Fan, E.; Bergman, L. W., Pyrazoleamide compounds are potent antimalarials that target Naþ homeostasis in intraerythrocytic Plasmodium falciparum, Nat. Commun., 5, 5521, (2014)
[102] Vaught, A., Graphing with Gnuplot and Xmgr: two graphing packages available under Linux, Linux J., 28es, 7, (1996)
[103] Verdonk, M. L.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.; Taylor, R. D., Improved protein-ligand docking using GOLD, Proteins Struct. Funct. Bioinf., 52, 609-623, (2003)
[104] Verdonk, M. L.; Berdini, V.; Hartshorn, M. J.; Mooij, W. T.; Murray, C. W.; Taylor, R. D.; Watson, P., Virtual screening using protein−ligand docking: avoiding artificial enrichment, J. Chem. Inf.and Comp. Sci, 44, 793-806, (2004)
[105] Wang, S. Q.; Du, Q. S.; Chou, K. C., Study of drug resistance of chicken influenza A virus (H5N1) from homology-modeled 3D structures of neuraminidases, Biochem. Biophys. Res. Commun., 354, 634-640, (2007)
[106] Wang, J. F.; Wei, D. Q.; Li, L.; Zheng, S. Y.; Li, Y. X.; Chou, K. C., 3D structure odeling of cytochrome P450 2C19 and its implication for personalized drug design, Biochem. Biophys. Res. Commun., 355, 513-519, (2007)
[107] Wang, S. Q.; Du, Q. S.; Huang, R. B.; Zhang, D. W.; Chou, K. C., Insights from investigating the interaction of oseltamivir (Tamiflu) with neuraminidase of the 2009 H1N1 swine flu virus, Biochem. Biophys. Res. Commun., 386, 432-436, (2009)
[108] Wang, J. F.; Chou, K. C., Insight into the molecular switch mechanism of human Rab5a from molecular dynamics simulations, Biochem. Biophysical Res. Comm., 390, 608-612, (2009)
[109] Wang, J. F.; Chou, K. C., Insights from studying the mutation-induced allostery in the M2 proton channel by molecular dynamics, Protein Eng. Des. Sel., 23, 663-666, (2010)
[110] Wang, J. F.; Chou, K. C., Insights from modeling the 3D structure of New Delhi metallo-β-lactamse and its binding interactions with antibiotic drugs, PLoS One, 6, 8414, (2011)
[111] Wang, J. F.; Chou, K. C., Insights into the mutation-induced HHH syndrome from modeling human mitochondrial ornithine transporter-1, PLoS One, 7, 31048, (2012)
[112] Wang, Y.; Coleman-Derr, D.; Chen, G.; Gu, Y. Q., OrthoVenn: a web server for genome-wide comparison and annotation of orthologous clusters across multiple species, Nucleic Acids Res, 43, W78-W84, (2015)
[113] Wass, M. N.; Kelley, L. A.; Sternberg, M. J., 3DLigandSite: predicting ligand-binding sites using similar structures, Nucleic Acids Res, 38, W469-W473, (2010)
[114] Webb, B.; Sali, A., Comparative protein structure modeling using MODELLER. Curr, Protoc. Bioinform., 47, 1-5, (2014)
[115] Wiederstein, M.; Sippl, M. J., ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins, Nucleic Acids Res, 35, W407-W410, (2007)
[116] Wernimont, A. K.; Amani, M.; Qiu, W.; Pizarro, J. C.; Artz, J. D.; Lin, Y. H.; Hui, R., Structures of parasitic CDPK domains point to a common mechanism of activation, Proteins Struct. Funct. Bioinf., 79, 803-820, (2011)
[117] Wernimont, A. K.; Artz, J. D.; Finerty, P.; Lin, Y. H.; Amani, M.; Allali-Hassani, A.; Chau, I., Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium, Nat. Stru. Mol. Biol., 17, 596, (2010)
[118] Zhang, V. M.; Chavchich, M.; Waters, N. C., Targeting protein kinases in the malaria parasite: update of an antimalarial drug target, Curr Top Med Chem, 12, 5, 456-472, (2012)
[119] Zhang, J.; Luan, C. H.; Chou, K. C.; Johnson, G. V., Identification of the N-terminal functional domains of Cdk5 by molecular truncation and computer modeling, Proteins Struct. Funct. Bioinf., 8, 447-453, (2002)
[120] Zhang, C. J.; Tang, H.; Li, W. C.; Lin, H.; Chen, W.; Chou, K. C., iOri-Human: identify human origin of replication by incorporating dinucleotide physicochemical properties into pseudo nucleotide composition, Oncotarget, 7, 69783, (2016)
[121] Zhang, M., Uncovering the essential genes of human malaria parasite Plasmodium falciparum by saturation mutagenesis, Science, 360, 6388, 1-10, (2018), 4
[122] Zhou, G. P., Biological functions of soliton and extra electron motion in DNA structure, Phys. Scr., 40, 698, (1989)
This reference list is based on information provided by the publisher or from digital mathematics libraries. Its items are heuristically matched to zbMATH identifiers and may contain data conversion errors. It attempts to reflect the references listed in the original paper as accurately as possible without claiming the completeness or perfect precision of the matching.