In Silico Approach for the Identification of Potential Targets and Specific Antimicrobials for Streptococcus mutans

Abstract

Tooth decay affects most of the population in developed countries. The multifactorial etiology of the disease includes multiple bacterial species, S. mutans is the main pathogen associated with the disease. This bacterium adheres to the tooth surface and allows the colonization of other microorganisms resulting in dental biofilm. Several therapeutic agents are available to treat or prevent tooth decay, but none, with the exception of fluoride, has significantly influenced the disease’s global burden. Moreover, the probable development of resistance of microorganisms to existing antibacterial agents and the scarcity of good antimicrobial agents motivates this effort for innovation. The detailed knowledge obtained in recent years on the S. mutans allowed the identification of potential targets in this microorganism, enabling the development of specific drugs to combat tooth decay. Thus, the identification of potential targets in these pathogens is the first step in the discovery process of new therapeutic agents. Currently, the experimental assays used for this purpose are expensive and time consuming. In contrast, bioinformatics methods to predict drug targets are cheap, quick and workaday in the biotechnology. This article will review the potential drug targets in S. mutans, as well as the bioinformatics methods used to identify these targets and effective drugs for specific pharmacological treatment of dental caries.

Share and Cite:

da Silva, A. , da Silva, D. , Macêdo Ferreira, S. , Agripino, G. , Albuquerque, A. and Rêgo, T. (2014) In Silico Approach for the Identification of Potential Targets and Specific Antimicrobials for Streptococcus mutans. Advances in Bioscience and Biotechnology, 5, 373-385. doi: 10.4236/abb.2014.54045.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Xu, X., Zhou, X.D. and Wu, C.D. (2011) The Tea Catechin Epigallocatechin Gallate Suppresses Cariogenic Factors of Streptococcus mutans. Antimicrob Agents Chemother, 55, 1229-1236. http://dx.doi.org/10.1128/AAC.01016-10
[2] Smith, D.J. and Taubman, M.A. (1996) Experimental Immunization of Rats with a Streptococcus Mutans 59 Kda Glucan Binding Protein Protects against Dental Caries. Infection and Immunity, 64, 3069-3073.
[3] Fejerskov, O. and Kidd, E., Eds. (2003) Dental Caries: The Disease and Its Clinical Management. Blackwell Monksgaard, Copenhagen.
[4] Loesche, W.J. (1986) Role of Streptococcus mutans in Human Dental Decay. Microbiology Reviews, 50, 353-380.
[5] Lewis, K. (2012) Persister Cells: Molecular Mechanisms Related to Antibiotic Tolerance. Handbook of Experimental Pharmacology, 211, 121-133. http://dx.doi.org/10.1007/978-3-642-28951-4_8
[6] Zeshi, Z., Nadezhina, E. and Wilkinson, K.J. (2010) Quantifying Diffusion in a Biofilm of Streptococcus mutans. Antimicrobial Agents and Chemotherapy, 55, 1075.
[7] Featherstone, J.D.B. (1999) Prevention and Reversal of Dental Caries: Role of Low Level Fluoride. Community Dentistry and Oral Epidemiology, 27, 31-40. http://dx.doi.org/10.1111/j.1600-0528.1999.tb01989.x
[8] Levine, M., Owen, W.L. and Avery, K.T. (2005) Anybody Response to Actinomyces Antigen and Dental Caries Experience: Implications for Caries Susceptibility. Clinical and Diagnostic Laboratory Immunology, 12, 764-769.
[9] Balakrishman, M., Simmonds, R.S. and Tagg J. (2000) Dental Caries Is a Preventable Infectious Disease. Australian Dental Journal, 45, 235-245. http://dx.doi.org/10.1111/j.1834-7819.2000.tb00257.x
[10] Russel, M.W., Childers, N.K., Michalek, S.M., Smith, D.J. and Taubman, M.A. (2004) A Caries Vaccine? The State of the Science of Immunization against Dental Caries. Caries Research, 38, 230-235.
[11] Guido, R.V.C. and Andricopulo, A.D. (2008) Modelagem Molecular de Fármacos. Revista Processos Químicos, 2, 24-26. http://www.rpqsenai.org.br/
[12] Andricopulo, A.D., Salum, L.B. and Abraham, D.J. (2009) Structure-Based Drug Design Strategies in Medicinal Chemistry. Current Topics in Medicinal Chemistry, 9, 771-790. http://dx.doi.org/10.2174/156802609789207127
[13] Marsh, P.D. (2004) Dental Plaque as a Microbial Biofilm. Caries Research, 38, 204-211.
http://dx.doi.org/10.1159/000077756
[14] Marsh, P.D. (1994) Microbial Ecology of Dental Plaque and Its Significance in Health and Disease. Advances in Dental Research, 8, 263-271.
[15] Socransky, S.S. and Haffajee, A.D. (2002) Dental Biofilms: Difficult Therapeutic Targets. Periodontology 2000, 28, 12-55. http://dx.doi.org/10.1034/j.1600-0757.2002.280102.x
[16] Butcher, S.P. (2003) Target Discovery and Validation in the Post-Genomic era. Neurochemical Research, 28, 367-371.
http://dx.doi.org/10.1023/A:1022349805831
[17] Da Silva, A.C.B. (2010) Effect of Chlorhexidine on the Gene Expression of Glucosyltransferase of Streptococcus mutans in Planktonic and Biofilm in Vitro Organized. Thesis PhD in Biotechnology Course of Federal University of Paraíba, João Pessoa, Paraíba.
[18] Koo, H., Xiao, J., Klein, M.I. and Jeon, J.G. (2010) Exopolysaccharides Produced by Streptococcus mutans Glucosyltransferases Modulate the Establishment ofMicrocolonies within Multispecies Biofilms. Journal of Bacteriology, 192, 3024-3032. http://dx.doi.org/10.1128/JB.01649-09
[19] Romling, U. and Balsalobre, C. (2012) Biofilm Infections, Their Resilience to Therapy and Innovative Treatment Strategies. Journal of Internal Medicine, 272, 541-561. http://dx.doi.org/10.1111/joim.12004
[20] Babpour, E., Angaji, S.A. and Angaji, S.M. (2009) Antimicrobial Effects of Four Medicinal Plants on Dental Plaque. Journal of Medicinal Plants Research, 3, 132-137.
[21] Michalek, S.M. and Childers, N.K. (1990) Developmental and Outlook for Caries Vaccine. Critical Reviews in Oral Biology and Medicine, 1, 37-54.
[22] Robinette, R.A., Oli, M.W., Mcarthur, W.P. and Brady, L.J. (2011) A Therapeutic Anti-Streptococcus mutans Monoclonal Antibody Used in Humanpassive Protection Trials Influences the Adaptive Immune Response. Vaccine, 29, 6292-6300. http://dx.doi.org/10.1016/j.vaccine.2011.06.027
[23] Featherstone, J.D.B. (2000) The Science and Practice of Caries Prevention. The Journal of the American Dental Association, 131, 887-899. http://dx.doi.org/10.14219/jada.archive.2000.0307
[24] Kubo, I., Muroi, H. and Himejima, M. (1993) Antimicrobial Activity against Streptococcus mutans of Mate Tea Flavor Components. Journal of Agricultural and Food Chemistry, 41, 107-111. http://dx.doi.org/10.1021/jf00025a023
[25] Tredwin, C.J., Scully, C. and Bagan-Sebastian, J.V. (2005) Drug-Induced Disorders of Teeth. Journal of Dental Research, 84, 596-602. http://dx.doi.org/10.1177/154405910508400703
[26] Singh, J., Kumar, A., Budhiaraja, S. and Hooda, A. (2007) Ethnomedicine: Use in Dental Caries. Brazilian Journal of Oral Sciences, 6, 1308-1312.
[27] Adonizio, A., Kong, K.F. and Mathee, K. (2008) Inhibition of Quorum Sensing-Controlled Virulence Factor Production in Pseudomonas aeruginosa by South Florida Plant Extracts. Antimicrobial Agents and Chemotherapy, 52, 198-203. http://dx.doi.org/10.1128/AAC.00612-07
[28] Hosseini, F., Adlgostar, A. and Sharifnia, F. (2013) Antibacterial Activity of Pistacia atlantica extracts on Streptococcus mutans Biofilm. International Research Journal of Biological Sciences, 2, 1-7.
[29] Al-Sohaibani, S. and Murugan, K. (2012) Anti-Biofilm Activity of Salvadora persica on Cariogenic Isolates of Streptococcus mutans: In Vitro and Molecular Docking Studies. Biofouling: The Journal of Bioadhesion and Biofilm Research, 28, 29-38.
[30] Iannitelli, A., Grande, R., Di Stefano, A., Di Giulio, M., Sozio, P., Bessa, L.J., Laserra, S., Paoloni, C., Protasi, F. and Cellini, L. (2011) Potential Antibacterial Activity of Carvacrol-Loadedpoly (DL-Lactide-co-Glycolide) (PLGA) Nanoparticles against Microbial Biofilm. International Journal of Molecular Sciences, 12, 5039-5051.
http://dx.doi.org/10.3390/ijms12085039
[31] Mahapatro, A. and Singh, D.K. (2011) Biodegradable Nanoparticles Are Excellent Vehicle for Site Directed in Vivo Delivery of Drugs and Vaccines. Journal of Nanobiotechnology, 9, 55. http://dx.doi.org/10.1186/1477-3155-9-55
[32] Milgrom, P., Zero, D.T. and Tanzer, J.M. (2009) An Examination of the Advances in Science and Technology of Prevention of Tooth Decay in Young Children since the Surgeon General’s Report on Oral Health. Academic Pediatrics, 9, 404-409. http://dx.doi.org/10.1016/j.acap.2009.09.001
[33] Cvitkovitch, D.G., Li, Y.H. and Ellen, R.P. (2003) Quorum Sensing and Biofilm Formation in Streptococcal Infections. Journal of Clinical Investigation, 112, 1626-1632. http://dx.doi.org/10.1172/JCI200320430
[34] Li, Y.H., Tang, N., Aspiras, M.B., Lau, P.C., Lee, J.H., Ellen, R.P. and Cvitkovitch, D.G. (2002) A Quorum-Sensing Signaling System Essential for Genetic Competence in Streptococcus mutans Is Involved in Biofilm Formation. Journal of Bacteriology, 184, 2699-2708. http://dx.doi.org/10.1128/JB.184.10.2699-2708.2002
[35] Liu, C., Worthington, R.J., Melander, C. and Wu, H. (2011) A New Small Molecule Specifically Inhibits the Cariogenic Bacterium Streptococcus mutans in Multispecies Biofilms. Antimicrobial Agents and Chemotherapy, 55, 2679-2687. http://dx.doi.org/10.1128/AAC.01496-10
[36] Smith, D.J., King, W.F., Barnes, L.A., Peacock, Z. and Taubman, M.A. (2003) Immunogenicity and Protective Immunity Induced by Synthetic Peptides Associated with Putative Immunodominant Regions of Streptococcus mutans Glucan-Binding Protein B. Infection and Immunity, 71, 1179-1184. http://dx.doi.org/10.1128/IAI.71.3.1179-1184.2003
[37] Len, A.C.L., Harty, D.W.S. and Jacques, N.A. (2004) Proteome Analysis of Streptococcus mutans Metabolic Phenotype during Acid Tolerance. Microbiology, 150, 1353-1366. http://dx.doi.org/10.1099/mic.0.26888-0
[38] Wang, P., Song, P., Mingming, J. and Guoping, Z. (2013) Isocitrate Dehydrogenase from Streptococcus mutans: Biochemical Properties and Evaluation of a Putative Phosphorylation Site at Ser102. PloS ONE, 8, e58918.
http://dx.doi.org/10.1371/journal.pone.0058918
[39] Quivey, R.G., Kuhnert, W. and Hahn, K. (2011) Genetics of Acid Adaptation in Oral Streptococci. Critical Reviews in Oral Biology & Medicine, 12, 301-314. http://dx.doi.org/10.1177/10454411010120040201
[40] Dashper, S.G. and Reynolds, E.C. (1992) pH Regulation by Streptococcus mutans. Journal of Dental Research, 71, 1159-1165. http://dx.doi.org/10.1177/00220345920710050601
[41] Amer, F.A., El-Behedy, E.M. and Mohtady, H.A. (2008) New Targets for Antibacterial Agents. Biotechnology and Molecular Biology Reviews, 3, 46-57.
[42] Wade, W.G. (2010) New Aspects and New Concepts of Maintaining “Microbiological” Health. Journal of Dentistry, 38, S21-S25. http://dx.doi.org/10.1016/S0300-5712(10)70007-5
[43] Hopkins, A.L. and Groom, C.R. (2002) The Druggable Genome. Nature Reviews Drug Discovery, 1, 727-730.
http://dx.doi.org/10.1038/nrd892
[44] Russ, A.P. and Lampel, S. (2005) The Druggable Genome: An Update. Drug Discovery Today, 10, 1607-1610.
http://dx.doi.org/10.1016/S1359-6446(05)03666-4
[45] An, J., Totrov, M. and Abagyan, R. (2004) Comprehensive Identification of “Druggable” Protein Ligand Binding Sites. Genome Informatics, 15, 31-41.
[46] Hajduk, P.J., Huth, J.R. and Tse, C. (2005) Predicting Protein Druggability. Drug Discovery Today, 10, 1675-1682.
http://dx.doi.org/10.1016/S1359-6446(05)03624-X
[47] Drews, J. (2000) Drug Discovery: A Historical Perspective. Science, 287, 1960-1964.
http://dx.doi.org/10.1126/science.287.5460.1960
[48] Overington, J.P., Al-Lazikani, B. and Hopkins, A.L. (2006) How Many Drug Targets Are There? Nature Reviews Drug Discovery, 5, 993-996. http://dx.doi.org/10.1038/nrd2199
[49] Betz, U.A. (2005) How Many Genomics Targets Can a Portfolio Afford? Drug Discovery Today, 10, 1057-1063.
http://dx.doi.org/10.1016/S1359-6446(05)03498-7
[50] Imming, P., Sinning, C. and Meyer, A. (2006) Drugs, Their Targets and the Nature and Number of Drug Targets. Nature Reviews Drug Discovery, 5, 821-834. http://dx.doi.org/10.1038/nrd2132
[51] De Magalhães, C.S. (2006) Algoritmos Genéticos para o Problema de Docking Proteína-Ligante. Tese de Doutorado do Curso de Modelagem Computacional do Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro.
[52] Vuong, C., Gerke, C., Somerville, G.A., Fischer, E.R. and Otto, M. (2003) Quorum-Sensing Control of Biofilm Factors in Staphylococcus epidermidis. Journal of Infectious Diseases, 188, 706-718. http://dx.doi.org/10.1086/377239
[53] Miller, M.B. and Bassler, B.L. (2001) Quorum Sensing in Bacteria. Annual Review of Microbiology, 55, 165-199.
http://dx.doi.org/10.1146/annurev.micro.55.1.165
[54] Stokes, N.R., Sievers, J., Barker, S., Bennett, J.M., Brown, D.R., Collins, I., Errington, V.M., Foulger, D., Hall, M., Halsey, R., Johnson, H., Rose, V., Thomaides, H.B., Haydon, D.J., Czaplewski, L.G. and Errington, J. (2005) Novel Inhibitors of Bacterial Cytokinesis Identified by a Cell-Based Antibiotic Screening Assay. Journal of Biological Chemistry, 48, 39709-39715. http://dx.doi.org/10.1074/jbc.M506741200
[55] Daughery, M., Vonstein, V., Overbeek, R. and Oserman, A. (2001) Archaeal Shikimate Kinase, a New Member of the GHMP-Kinase Family. Journal of Bacteriology, 183, 292-300. http://dx.doi.org/10.1128/JB.183.1.292-300.2001
[56] Zhang, Y.M., White, S.W. and Rock, C.O. (2006) Inhibiting Bacterial Fatty Acid Synthesis. Journal of Biological Chemistry, 281, 17541-17544. http://dx.doi.org/10.1074/jbc.R600004200
[57] Whiteley, M., Bangera, M.G., Bumgarner, R.E., Parsek, M.R., Teitzel, G.M., Lory, S. and Greenberg, E.P. (2001) Gene Expression in Pseudomonas aeruginosa Biofilms. Nature, 413, 860-864. http://dx.doi.org/10.1038/35101627
[58] Motegi, M., Takagi, Y., Yonezawa, H., Hanada, N., Terajima, J., Watanabe, H. and Senpuku, H. (2006) Assessment of Genes Associated with Streptococcus mutans Biofilm Morphology. Applied and Environmental Microbiology, 72, 6277-6287. http://dx.doi.org/10.1128/AEM.00614-06
[59] Yamashita, Y., Bowen, W.H., Burne, R.A. and Kuramitsu, H.K. (1993) Role of the Streptococcus mutans gtf Genes in Caries Induction in the Specific-Pathogen-Free Rat Model. Infection and Immunity, 61, 3811-3817.
[60] Wen, Z.T. and Burne, R.A. (2002) Functional Genomics Approach to Identifying Genes Required for Biofilm Development by Streptococcus mutans. Applied and Environmental Microbiology, 68, 1196-1203.
http://dx.doi.org/10.1128/AEM.68.3.1196-1203.2002
[61] Merritt, J., Qi, F., Goodman, S.D., Anderson, M.H. and Shi, W. (2003) Mutation of luxS Affects Biofilm Formation in Streptococcus mutans. Infection and Immunity, 71, 1972-1979. http://dx.doi.org/10.1128/IAI.71.4.1972-1979.2003
[62] Helmann, J.D., Wu, M.F.W., Kobel, P.A., Gamo, F.J., Wilson, M., Morshedi, M.M., Navre, M. and Paddon, C. (2001) Global Transcriptional Response of Bacillus subtilis to Heat Shock. Journal of Bacteriology, 183, 7318-7328.
http://dx.doi.org/10.1128/JB.183.24.7318-7328.2001
[63] DeLisa, M.P., Wu, C.F., Wang, L., Valdes, J.J. and Bentley, W.E. (2001) DNA Microarray-Based Identification of Genes Controlled by Autoinducer 2-Stimulated Quorum Sensing in Escherichia coli. Journal of Bacteriology, 183, 5239-5247. http://dx.doi.org/10.1128/JB.183.18.5239-5247.2001
[64] Ye, R.W., Tao, W., Bedzyk, L., Young, T., Chen, M. and Li, L. (2000) Global Gene Expression Profiles of Bacillus subtilis Grown under Anaerobic Conditions. Journal of Bacteriology, 182, 4458-4465.
http://dx.doi.org/10.1128/JB.182.16.4458-4465.2000
[65] Fawcett, P., Eichenberger, P., Losick, R. and Youngman, P. (2000) The Transcriptional Profile of Early to Middle Sporulation in Bacillus subtilis. Proceedings of the National Academy of Sciences of the United States of America, 97, 8063-8068. http://dx.doi.org/10.1073/pnas.140209597
[66] Ajdic, D., McShan, W.M., McLaughlin, R.E., Savic, G., Chang, J., Carson, M.B., Primeaux, C., Tian, R.Y., Kenton, S., Jia, H.G., Lin, S.P., Qian, Y.D., Li, S.L., Zhu, H., Najar, F., Lai, H.S., White, J. and Roe, B.A. (2002) Genome Sequence of Streptococcus mutans UA159, a Cariogenic Dental Pathogen. Proceedings of the National Academy of Sciences of the United States of America, 99, 14434-14439. http://dx.doi.org/10.1073/pnas.172501299
[67] Marsh, P.D. (2010) Controlling the Oral Biofilm with Antimicrobials. Journal of Dentistry, 38, S11-S15.
http://dx.doi.org/10.1016/S0300-5712(10)70005-1
[68] Galperin, M.Y. (2010) Diversity of Structure and Function of Response Regulator Output Domains. Current Opinion in Microbiology, 13, 150-159. http://dx.doi.org/10.1016/j.mib.2010.01.005
[69] Al-Sohaibani, S. and Murugan, K. (2012) Anti-Biofilm Activity of Salvadora persica on Cariogenic Isolates of Streptococcus mutans: In Vitro and Molecular Docking Studies. Biofouling: The Journal of Bioadhesion and Biofilm Research, 28, 29-38.
[70] Cooper, R. and Okhiria, O. (2006) Biofilms, Wound Infection and the Issue of Control. Wounds, 2, 48-57.
[71] Kumar, C., et al. (2013) An in Silico Study of Quinic Acid Derivatives as Inhibitors of Com A, the Quorum Sensing Protein of Streptococcus mutans Responsible for the Pathogenesis in Dental Caries. International Journal of Biotechnology and Allied Fields, 1, 76-84. http://www.ijbaf.com/
[72] Aguero, F., Al-Lazikani, B., Aslett, M., Berriman, M., Buckner, F.S., Campbell, R.K., Carmona, S., Carruthers, I.M., Edith Chan, A.W., Chen, F., Crowther, G.J., Doyle, M.A., Hertz-Fowler, C., Hopkins, A.L., McAllister, G., Nwaka, S., Overington, J.P., Pain, A., Paolini, G.V., Pieper, U., Ralph, S.A., Riechers, A., Roos, D.S., Sali, A., Shanmugam, D., Suzuki, T., Van Voorhis, W.C. and Verlinde, C.L.M.J. (2008) Genomic-Scale Prioritization of Drug Targets: The TDR Targets Database. Nature Reviews Drug Discovery, 7, 900-907. http://dx.doi.org/10.1038/nrd2684
[73] Horst, J.A., Laurenzi, A., Bernard, B. and Samudrala, R. (2012) Computational Multitarget Drug Discovery. In: Peters, J.E., Ed., Polypharmacology, John Wiley and Sons Publishing Co., Hoboken, 236-302.
[74] Dutta, C. and Pan, A. (2002) Horizontal Gene Transfer and Bacterial Diversity. Journal of Biosciences, 27, 27-33.
http://dx.doi.org/10.1007/BF02703681
[75] Skippington, E. and Ragan, M.A. (2011) Lateral Genetic Transfer and the Construction of Genetic Exchange Communities. FEMS Microbiology Reviews, 35, 707-735. http://dx.doi.org/10.1111/j.1574-6976.2010.00261.x
[76] Langille, M.G., Hsiao, W.W. and Brinkman, F.S. (2010) Detecting Genomic Islands Using Bioinformatics Approaches. Nature Reviews Microbiology, 8, 373-382. http://dx.doi.org/10.1038/nrmicro2350
[77] Gogarten, J.P., Doolittle, W.F. and Lawrence, J.G. (2002) Prokaryotic Evolution in Light of Gene Transfer. Molecular Biology and Evolution, 19, 2226-2238. http://dx.doi.org/10.1093/oxfordjournals.molbev.a004046
[78] Hasan, M.S., Liu, Q., Wang, H., Fazekas, J., Chen, B. and Che, D. (2012) GIST: Genomic Island Suite of Tools for Predicting Genomic Islands in Genomic Sequences. Bioinformation, 8, 203-205.
http://dx.doi.org/10.6026/97320630008203
[79] Nan, J., Brostromer, E., Liu, X., Kristensen, O. and Su, X. (2009) Bioinformatics and Structural Characterization of a Hypothetical Protein from Streptococcus mutans: Implication of Antiobiotic Resistance. PLoS ONE, 4, e7245.
http://dx.doi.org/10.1371/journal.pone.0007245
[80] Venselaar, H., Joosten, R.P., Vroling, B., Baakman, C.A., Hekkelman, M.L., Krieger, E. and Vriend, G. (2010) Homology Modelling and Spectroscopy, a Never-Ending Love Story. European Biophysics Journal, 39, 551-563.
http://dx.doi.org/10.1007/s00249-009-0531-0
[81] Aqvist, J. and Marelius, J. (2001) The Linear Interaction Energy Method for Predicting Ligand Binding Free Energies. Combinatorial Chemistry & High Throughput Screening, 4, 613-626. http://dx.doi.org/10.2174/1386207013330661
[82] Brooijmans, N. and Kuntz, I.D. (2003) Molecular Recognition and Docking Algorithms. Annual Review of Biophysics and Biomolecular Structure, 32, 335-373. http://dx.doi.org/10.1146/annurev.biophys.32.110601.142532
[83] Robertson, J.G. (2005) Mechanistic Basis of Enzyme-Targeted Drugs. Biochemistry, 44, 5561-5571.
http://dx.doi.org/10.1021/bi050247e
[84] Leach, A.R., Shoichet, B.K. and Peishoff, C.E. (2006) Docking and Scoring-Perspective. Journal of Medicinal Chemistry, 49, 5851-5855. http://dx.doi.org/10.1021/jm060999m
[85] Apostolakis, J. and Caflisch, A. (1999) Computational Ligand Design. Combinatorial Chemistry & High Throughput Screening, 2, 91-104.
[86] Trosset, J.Y. and Scheraga, H.A. (1998) Reaching the Global Minimum in Docking Simulations: A Monte Carlo Energy Minimization Approach Using Bezier Splines. Proceedings of the National Academy of Sciences of the United States of America, 95, 8011-8015. http://dx.doi.org/10.1073/pnas.95.14.8011
[87] Case, D.A., Cheatham III, T.E., Darden, T., Gohlke, H., Luo, R., Merz Jr., K.M., Onufriev, A., Simmerling, C., Wang, B. and Woods, R.J. (2005) The Amber Biomolecular Simulation Programs. Journal of Computational Chemistry, 26, 1668-1688. http://dx.doi.org/10.1002/jcc.20290
[88] Leach, A.R. (2001) Molecular Modeling: Principles and Applications. 2nd Edition, Pearson Education Ltda, Upper Saddle River.
[89] van Gunsteren, W.F. and Berendsen, H.J.C. (1987) GROMOS-87 Manual. Biomos BV Nijenborgh 4, 9747 AG, Groningen.
[90] Weiner, S.J., Kollman, P.A., Case, D.A., Chandra Singh, U., Ghio, C., Alagona, G., Profeta, S. and Weiner, P. (1984) A New Force Field for Molecular Mechanical Simulation of Nucleic Acids and Proteins. Journal of American Chemical Society, 106, 765-784. http://dx.doi.org/10.1021/ja00315a051
[91] Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Merz Jr., K.M., Fergunson, D.M., Spellmeyer, D.C., Fox, T., Caldwell, J.W. and Kollman, P.A. (1995) A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids and Organic Molecules. Journal of the American Chemical Society, 117, 5179-5197.
http://dx.doi.org/10.1021/ja00124a002
[92] Brooks, B.R., Bruccoreli, R.E., Olafson, B.D., States, D.J., Swaminathan, S. and Karplus, M. (1983) CHARMM: A Program for Macromolecular Energy Minimization and Dynamics Calculation. Journal of Computacional Chemistry, 4, 187-217. http://dx.doi.org/10.1002/jcc.540040211
[93] Halgren, T.A. (1996) Merck Molecular Force Field. I. Basis, Form, Scope, Parameterization, and Performance of MMFF94. Journal of Computational Chemistry, 17, 490-519.
http://dx.doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<490::AID-JCC1>3.0.CO;2-P
[94] Halgren T.A. (1996) Merck Molecular Force Field. II. MMFF94 van der Waals and Electrostatic Parameters for Intermolecular Interactions. Journal of Computational Chemistry, 17, 520-552.
http://dx.doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<520::AID-JCC2>3.0.CO;2-W
[95] Halgren, T.A. (1996) Merck Molecular Force Field. III. Molecular Geometries and Vibrational Frequencies for MMFF94. Journal of Computational Chemistry, 17, 553-586.
http://dx.doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<553::AID-JCC3>3.0.CO;2-T
[96] Halgren, T.A. (1996) Merck Molecular Force Field. IV. Conformational Energies and Geometries for MMFF94. Journal of Computational Chemistry, 17, 587-615.
http://dx.doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<587::AID-JCC4>3.0.CO;2-Q
[97] Halgren, T.A. (1996) Merck Molecular Force Field. V. Extension of MMFF94 Using Experimental Data, Additional Computational Data and Empirical Rules. Journal of Computacional Chemistry, 17, 616-641.
http://dx.doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<616::AID-JCC5>3.0.CO;2-X
[98] Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A.E. and Berendsen, H.J. (2005) GROMACS: Fast, Flexible, and Free. Journal of Computacional Chemistry, 26, 1701-1718. http://dx.doi.org/10.1002/jcc.20291
[99] Brooks, B.R., Brooks III, C.L., Mackerell Jr., A.D., Nilsson, L., Petrella, R.J., Roux, B., Won, Y., Archontis, G., Bartels, C., Boresch, S., Caflisch, A., Caves, L., Cui, Q., Dinner, A.R., Feig, M., Fischer, S., Gao, J., Hodoscek, M., Im, W. and Kuczer, K. (2009) CHARMM: The Biomolecular Simulation Program. Journal of Computacional Chemistry, 30, 1545-1614. http://dx.doi.org/10.1002/jcc.21287
[100] Frisch, M.J., Trucks, G.W., Schlegel, H.B., et al. (1998) Gaussian 98. Gaussian Inc., Pittsburgh.
[101] Schmidt, M.W., Baldridge, K.K., Boatz, J.A., Elbert, S.T., Gordon, M.S., Jensen, J.H., Koseki, S., Matsunaga, N., Nguyen, K.A., Su, S.J., Windus, T.L., Dupuis, M. and Montgomery Jr., J.A. (1993) General Atomic and Molecular Electronic Structure System. Journal of Computational Chemistry, 14, 1347-1363. http://dx.doi.org/10.1002/jcc.540141112
[102] Deppmeier, B., Driesse, A.J., et al. (2000) Wavefunction Inc., Irvine.
[103] Schneider, G. and Böhm, H.J. (2002) Virtual Screening and Fast Automated Docking Methods. Drug Discovery Today, 7, 64-70. http://dx.doi.org/10.1016/S1359-6446(01)02091-8
[104] Walum, E., Hedander, J. and Garberg, P. (2005) On the Relevance of Cytotoxicity Measurements, Barrier Passage Determinations and High Throughput Screening in Vitro to Select Potentially Hazardous Compounds in Large Sets of Chemicals. Toxicology and Applied Pharmacology, 207, 393-397.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.