{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:42:17Z","timestamp":1767962537410,"version":"3.49.0"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,9,14]],"date-time":"2015-09-14T00:00:00Z","timestamp":1442188800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2015,9,14]],"date-time":"2015-09-14T00:00:00Z","timestamp":1442188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Biochem Biophys"],"published-print":{"date-parts":[[2016,3]]},"DOI":"10.1007\/s12013-015-0709-2","type":"journal-article","created":{"date-parts":[[2015,9,14]],"date-time":"2015-09-14T16:20:32Z","timestamp":1442247632000},"page":"35-48","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Single Active Site Mutation Causes Serious Resistance of HIV Reverse Transcriptase to Lamivudine: Insight from Multiple Molecular Dynamics Simulations"],"prefix":"10.1007","volume":"74","author":[{"given":"Suri","family":"Moonsamy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumendranath","family":"Bhakat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross C.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud E. S.","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,9,14]]},"reference":[{"issue":"2","key":"709_CR1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1111\/j.1467-7679.2007.00367.x","volume":"25","author":"EU Morah","year":"2007","unstructured":"Morah, E. U. (2007). Are people aware of their HIV-positive status responsible for driving the epidemic in subsaharan Africa? The case of Malawi. Development Policy Review, \n                           25(2), 215\u2013242.","journal-title":"Development Policy Review"},{"key":"709_CR2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.2174\/1568005024605873","volume":"2","author":"A Pani","year":"2002","unstructured":"Pani, A., Loi, A. G., Mura, M., Marceddu, T., La Colla, P., & Marongiu, M. E. (2002). Targeting HIV: Old and new players. Current Drug Target Infectious Disorders, \n                           2, 17\u201332.","journal-title":"Current Drug Target Infectious Disorders"},{"key":"709_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/586401","volume":"2012","author":"F Esposito","year":"2012","unstructured":"Esposito, F., Corona, A., & Tramontano, E. (2012). HIV-1 reverse transcriptase still remains a new drug target: Structure function, classical inhibitors, and new inhibitors with innovative mechanisms of actions. Molecular Biology International, \n                           2012, 1\u201323.","journal-title":"Molecular Biology International"},{"key":"709_CR4","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.antiviral.2006.09.003","volume":"72","author":"RF Schinazi","year":"2006","unstructured":"Schinazi, R. F., Hernandez-Santiago, B. I., & Hurwitz, S. J. (2006). Pharmacology of current and promising nucleosides for the treatment of human immunodeficiency viruses (vol 71, pg 322, 2006). Antiviral Research, \n                           72, 256.","journal-title":"Antiviral Research"},{"key":"709_CR5","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3390\/biology1030521","volume":"1","author":"T Ilina","year":"2012","unstructured":"Ilina, T., LaBarge, K., Sarafianos, S. G., Ishima, R., & Parniak, M. A. (2012). Inhibitors of HIV-1 reverse transcriptase\u2014associated ribonuclease H activity. Biology, \n                           1, 521\u2013541.","journal-title":"Biology"},{"key":"709_CR6","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s00018-005-5367-x","volume":"63","author":"V Vivet-Boudou","year":"2006","unstructured":"Vivet-Boudou, V., Didierjean, J., Isel, C., & Marquet, R. (2006). Nucleoside and nucleotide inhibitors of HIV-1 replication. Cellular and Molecular Life Sciences, \n                           63, 163\u2013186.","journal-title":"Cellular and Molecular Life Sciences"},{"key":"709_CR7","doi-asserted-by":"publisher","first-page":"5083","DOI":"10.1093\/nar\/gkn464","volume":"36","author":"JD Bauman","year":"2008","unstructured":"Bauman, J. D., Das, K., Ho, W. C., Baweja, M., Himmel, D. M., Clark, A. D, Jr, et al. (2008). Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design. Nucleic Acids Research, \n                           36, 5083\u20135092.","journal-title":"Nucleic Acids Research"},{"key":"709_CR8","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1128\/CDLI.10.6.979-981.2003","volume":"10","author":"D Turner","year":"2003","unstructured":"Turner, D., Brenner, B., & Wainberg, M. A. (2003). Multiple effects of the M184V resistance mutation in the reverse transcriptase of human immunodeficiency virus type 1. Clinical and Diagnostic Laboratory Immunology, \n                           10, 979\u2013981.","journal-title":"Clinical and Diagnostic Laboratory Immunology"},{"issue":"2","key":"709_CR9","first-page":"113","volume":"7","author":"AS Ray","year":"2005","unstructured":"Ray, A. S. (2005). Intracellular interactions between nucleos(t)ide inhibitors of HIV reverse transcriptase. AIDS Reviews, \n                           7(2), 113\u2013125.","journal-title":"AIDS Reviews"},{"key":"709_CR10","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/S1473-3099(13)70127-0","volume":"13","author":"RL Hamers","year":"2013","unstructured":"Hamers, R. L., Kityo, C., Sigaloff, K. C., & de Wit, T. F. R. (2013). Pretreatment HIV-1 drug resistance in Africa. Lancet Infectious Diseases, \n                           13, 476.","journal-title":"Lancet Infectious Diseases"},{"key":"709_CR11","doi-asserted-by":"publisher","first-page":"S36","DOI":"10.1097\/01.qai.0000137005.63376.6e","volume":"37","author":"MA Wainberg","year":"2004","unstructured":"Wainberg, M. A., & Turner, D. (2004). Resistance issues with new nucleoside\/nucleotide backbone options. JAIDS Journal of Acquired Immune Deficiency Syndromes, \n                           37, S36\u2013S43.","journal-title":"JAIDS Journal of Acquired Immune Deficiency Syndromes"},{"key":"709_CR12","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1006\/jmbi.2000.3823","volume":"300","author":"HQ Gao","year":"2000","unstructured":"Gao, H. Q., Boyer, P. L., Sarafianos, S. G., Arnold, E., & Hughes, S. H. (2000). The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase. Journal of Molecular Biology, \n                           300, 403\u2013418.","journal-title":"Journal of Molecular Biology"},{"key":"709_CR13","doi-asserted-by":"publisher","first-page":"10027","DOI":"10.1073\/pnas.96.18.10027","volume":"96","author":"SG Sarafianos","year":"1999","unstructured":"Sarafianos, S. G., Das, K., Clark, A. D., Ding, J. P., Boyer, P. L., Hughes, S. H., & Arnold, E. (1999). Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. Proceedings of the National Academy of Sciences of the United States of America, \n                           96, 10027\u201310032.","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"709_CR14","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1080\/07391102.2013.803264","volume":"32","author":"R Purohit","year":"2014","unstructured":"Purohit, R. (2014). Role of ELA region in auto-activation of mutant KIT receptor: A molecular dynamics simulation insight. Journal of Biomolecular Structure and Dynamics, \n                           32, 1033\u20131046.","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"709_CR15","doi-asserted-by":"publisher","DOI":"10.1021\/cr300314q","author":"H Bahareh","year":"2013","unstructured":"Bahareh, H., Govender, T., Maguire, G. E. M., Soliman, M. E. S., & Kruger, H. G. (2013). Integrated approach to structure-based enzymatic drug design: molecular modeling, spectroscopy, and experimental bioactivity. Chemical Reviews,. doi:\n                    10.1021\/cr300314q\n                    \n                  .","journal-title":"Chemical Reviews"},{"key":"709_CR16","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1080\/07391102.2011.10507379","volume":"29","author":"R Purohit","year":"2011","unstructured":"Purohit, R., Rajendran, V., & Sethumadhavan, R. (2011). Studies on adaptability of binding residues and flap region of TMC-114 resistance HIV-1 protease mutants. Journal of Biomolecular Structure and Dynamics, \n                           29, 137\u2013152.","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"709_CR17","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s00726-011-1108-7","volume":"43","author":"V Rajendran","year":"2012","unstructured":"Rajendran, V., Purohit, R., & Sethumadhavan, R. (2012). In silico investigation of molecular mechanism of laminopathy caused by a point mutation (R482W) in lamin A\/C protein. Amino Acids, \n                           43, 603\u2013615.","journal-title":"Amino Acids"},{"key":"709_CR18","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1007\/s00894-010-0785-6","volume":"17","author":"R Purohit","year":"2011","unstructured":"Purohit, R., Rajendran, V., & Sethumadhavan, R. (2011). Relationship between mutation of serine residue at 315th position in M. tuberculosis catalase-peroxidase enzyme and isoniazid susceptibility: An in silico analysis. Journal of Molecular Modeling, \n                           17, 869\u2013877.","journal-title":"Journal of Molecular Modeling"},{"key":"709_CR19","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1007\/s12013-013-9551-6","volume":"67","author":"K Balu","year":"2013","unstructured":"Balu, K., Rajendran, V., Sethumadhavan, R., & Purohit, R. (2013). Investigation of binding phenomenon of NSP3 and p130Cas mutants and their effect on cell signalling. Cell Biochemistry and Biophysics, \n                           67, 623\u2013633.","journal-title":"Cell Biochemistry and Biophysics"},{"key":"709_CR20","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1080\/07391102.2012.759885","volume":"32","author":"V Rajendran","year":"2014","unstructured":"Rajendran, V., & Sethumadhavan, R. (2014). Drug resistance mechanism of PncA in Mycobacterium tuberculosis. Journal of Biomolecular Structure and Dynamics, \n                           32, 209\u2013221.","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"709_CR21","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1021\/ci060090c","volume":"46","author":"O Aruksakunwong","year":"2006","unstructured":"Aruksakunwong, O., Wolschann, P., Hannongbua, S., & Sompornpisut, P. (2006). Molecular dynamic and free energy studies of primary resistance mutations in HIV-1 protease-ritonavir complexes. Journal of Chemical Information and Modeling, \n                           46, 2085\u20132092.","journal-title":"Journal of Chemical Information and Modeling"},{"key":"709_CR22","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1021\/jm0609162","volume":"50","author":"TJ Hou","year":"2007","unstructured":"Hou, T. J., & Yu, R. (2007). Molecular dynamics and free energy studies on the wild-type and double mutant HIV-1 protease complexed with amprenavir and two amprenavir-related inhibitors: Mechanism for binding and drug resistance. Journal of Medicinal Chemistry, \n                           50, 1177\u20131188.","journal-title":"Journal of Medicinal Chemistry"},{"key":"709_CR23","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1021\/ja0779250","volume":"130","author":"I Stoica","year":"2008","unstructured":"Stoica, I., Sadiq, S. K., & Coveney, P. V. (2008). Rapid and accurate prediction of binding free energies for saquinavir-bound HIV-1 proteases. Journal of the American Chemical Society, \n                           130, 2639\u20132648.","journal-title":"Journal of the American Chemical Society"},{"key":"709_CR24","doi-asserted-by":"publisher","first-page":"17253","DOI":"10.1021\/ja053973d","volume":"127","author":"ZG Zhou","year":"2005","unstructured":"Zhou, Z. G., Madrid, M., Evanseck, J. D., & Madura, J. D. (2005). Effect of a bound non-nucleoside RT inhibitor on the dynamics of wild-type and mutant HIV-1 reverse transcriptase. Journal of the American Chemical Society, \n                           127, 17253\u201317260.","journal-title":"Journal of the American Chemical Society"},{"key":"709_CR25","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1039\/c2mb25114k","volume":"8","author":"WW Xue","year":"2012","unstructured":"Xue, W. W., Qi, J., Yang, Y., Jin, X. J., Liu, H. X., & Yao, X. J. (2012). Understanding the effect of drug-resistant mutations of HIV-1 intasome on raltegravir action through molecular modeling study. Molecular BioSystems, \n                           8, 2135\u20132144.","journal-title":"Molecular BioSystems"},{"key":"709_CR26","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1021\/ct800068v","volume":"4","author":"R Chachra","year":"2008","unstructured":"Chachra, R., & Rizzo, R. C. (2008). Origins of resistance conferred by the R292K neuraminidase mutation via molecular dynamics and free energy calculations. Journal of Chemical Theory and Computation, \n                           4, 1526\u20131540.","journal-title":"Journal of Chemical Theory and Computation"},{"key":"709_CR27","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1021\/mp100041b","volume":"7","author":"HX Liu","year":"2010","unstructured":"Liu, H. X., Yao, X. J., Wang, C. Q., & Han, J. A. (2010). In silico identification of the potential drug resistance sites over 2009 influenza A (H1N1) virus neuraminidase. Molecular Pharmaceutics, \n                           7, 894\u2013904.","journal-title":"Molecular Pharmaceutics"},{"key":"709_CR28","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1021\/ct600151y","volume":"2","author":"ZY Guo","year":"2006","unstructured":"Guo, Z. Y., Prongay, A., Tong, X., Fischmann, T., Bogen, S., Velazquez, F., et al. (2006). Computational study of the effects of mutations A156T, D168V, and D168Q on the binding of HCV protease inhibitors. Journal of Chemical Theory and Computation, \n                           2, 1657\u20131663.","journal-title":"Journal of Chemical Theory and Computation"},{"key":"709_CR29","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1016\/j.bbagen.2012.06.001","volume":"1820","author":"DB Pan","year":"2012","unstructured":"Pan, D. B., Xue, W. W., Zhang, W. Q., Liu, H. X., & Yao, X. J. (2012). Understanding the drug resistance mechanism of hepatitis C virus NS3\/4A to ITMN-191 due to R155K, A156V, D168A\/E mutations: A computational study. Biochimica Et Biophysica Acta General Subjects, \n                           1820, 1526\u20131534.","journal-title":"Biochimica Et Biophysica Acta General Subjects"},{"key":"709_CR30","doi-asserted-by":"publisher","first-page":"8220","DOI":"10.1021\/jp045437y","volume":"109","author":"XL Cheng","year":"2005","unstructured":"Cheng, X. L., Cui, G. L., Hornak, V., & Sinnnerling, C. (2005). Modified replica exchange simulation methods for local structure refinement. Journal of Physical Chemistry B, \n                           109, 8220\u20138230.","journal-title":"Journal of Physical Chemistry B"},{"key":"709_CR31","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1021\/ct050250b","volume":"2","author":"R Affentranger","year":"2006","unstructured":"Affentranger, R., Tavernelli, I., & Di Iorio, E. E. (2006). A novel Hamiltonian replica exchange MD protocol to enhance protein conformational space sampling. Journal of Chemical Theory and Computation, \n                           2, 217\u2013228.","journal-title":"Journal of Chemical Theory and Computation"},{"key":"709_CR32","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1021\/ct050196z","volume":"2","author":"A Okur","year":"2006","unstructured":"Okur, A., Wickstrom, L., Layten, M., Geney, R., Song, K., Hornak, V., & Simmerling, C. (2006). Improved efficiency of replica exchange simulations through use of a hybrid explicit\/implicit solvation model. Journal of Chemical Theory and Computation, \n                           2, 420\u2013433.","journal-title":"Journal of Chemical Theory and Computation"},{"key":"709_CR33","doi-asserted-by":"publisher","first-page":"13749","DOI":"10.1073\/pnas.0506346102","volume":"102","author":"P Liu","year":"2005","unstructured":"Liu, P., Kim, B., Friesner, R. A., & Berne, B. J. (2005). Replica exchange with solute tempering: A method for sampling biological systems in explicit water. Proceedings of the National Academy of Sciences of the United States of America, \n                           102, 13749\u201313754.","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"709_CR34","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.jmb.2008.10.018","volume":"385","author":"GG Maisuradze","year":"2009","unstructured":"Maisuradze, G. G., Liwo, A., & Scheraga, H. A. (2009). Principal component analysis for protein folding dynamics. Journal of Molecular Biology, \n                           385, 312\u2013329.","journal-title":"Journal of Molecular Biology"},{"key":"709_CR35","doi-asserted-by":"publisher","first-page":"L01","DOI":"10.1016\/j.bpj.2012.05.002","volume":"103","author":"JR Thomas","year":"2012","unstructured":"Thomas, J. R., Gedeon, P. C., Grant, B. J., & Madura, J. D. (2012). LeuT conformational sampling utilizing accelerated molecular dynamics and principal component analysis. Biophysical Journal, \n                           103, L01\u2013L03.","journal-title":"Biophysical Journal"},{"key":"709_CR36","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1080\/07391102.1996.10508874","volume":"13","author":"A Amadei","year":"1996","unstructured":"Amadei, A., Linssen, A. B., de Groot, B. L., van Aalten, D. M., & Berendsen, H. J. (1996). An efficient method for sampling the essential subspace of proteins. Journal of Biomolecular Structure and Dynamics, \n                           13, 615\u2013625.","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"709_CR37","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1093\/protein\/8.11.1129","volume":"8","author":"DM van Aalten","year":"1995","unstructured":"van Aalten, D. M., Findlay, J. B., Amadei, A., & Berendsen, H. J. (1995). Essential dynamics of the cellular retinol-binding protein\u2014Evidence for ligand-induced conformational changes. Protein Engineering Design and Selection, \n                           8, 1129\u20131135.","journal-title":"Protein Engineering Design and Selection"},{"key":"709_CR38","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1002\/prot.340170408","volume":"17","author":"A Amadei","year":"1993","unstructured":"Amadei, A., Linssen, A. B. M., & Berendsen, H. J. C. (1993). Essential dynamics of proteins. Proteins: Structure Function, and Bioinformatics, \n                           17, 412\u2013425.","journal-title":"Proteins: Structure Function, and Bioinformatics"},{"key":"709_CR39","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1006\/jmbi.1998.2400","volume":"285","author":"JM Word","year":"1999","unstructured":"Word, J. M., Lovell, S. C., LaBean, T. H., Taylor, H. C., Zalis, M. E., Presley, B. K., et al. (1999). Visualizing and quantifying molecular goodness-of-fit: Small-probe contact dots with explicit hydrogen atoms. Journal of Molecular Biology, \n                           285, 1711\u20131733.","journal-title":"Journal of Molecular Biology"},{"key":"709_CR40","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/S0959-440X(94)90321-2","volume":"4","author":"DA Case","year":"1994","unstructured":"Case, D. A. (1994). Normal-mode analysis of protein dynamics. Current Opinion in Structural Biology, \n                           4, 285\u2013290.","journal-title":"Current Opinion in Structural Biology"},{"key":"709_CR41","doi-asserted-by":"publisher","first-page":"4995","DOI":"10.1073\/pnas.82.15.4995","volume":"82","author":"B Brooks","year":"1985","unstructured":"Brooks, B., & Karplus, M. (1985). Normal-modes for specific motions of macromolecules\u2014Application to the Hinge-Bending mode of lysozyme. Proceedings of the National Academy of Sciences of the United States of America, \n                           82, 4995\u20134999.","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"6","key":"709_CR42","doi-asserted-by":"publisher","first-page":"e1002068","DOI":"10.1371\/journal.pcbi.1002068","volume":"7","author":"E Laine","year":"2011","unstructured":"Laine, E., de Beauchene, I. C., Perahia, D., Auclair, C., & Tchertanov, L. (2011). Mutation D816V alters the internal structure and dynamics of c-KIT receptor cytoplasmic region: Implications for dimerization and activation mechanisms. PLoS Computational Biology, \n                           7(6), e1002068\u2013e1002068.","journal-title":"PLoS Computational Biology"},{"key":"709_CR43","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1089\/10665270360688228","volume":"10","author":"ML Teodoro","year":"2003","unstructured":"Teodoro, M. L., Phillips, G. N., & Kavraki, L. E. (2003). Understanding protein flexibility through dimensionality reduction. Journal of Computational Biology, \n                           10, 617\u2013634.","journal-title":"Journal of Computational Biology"},{"key":"709_CR44","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.str.2007.12.011","volume":"16","author":"L Yang","year":"2008","unstructured":"Yang, L., Song, G., Carriquiry, A., & Jernigan, R. L. (2008). Close correspondence between the motions from principal component analysis of multiple HIV-1 protease structures and elastic network modes. Structure, \n                           16, 321\u2013330.","journal-title":"Structure"},{"key":"709_CR45","doi-asserted-by":"publisher","unstructured":"del Sol, A., Fujihashi, H., Amoros, D., & Nussinov, R. (2006). Residues crucial for maintaining short paths in network communication mediate signaling in proteins. Molecular Systems Biology, 2. doi:\n                    10.1038\/msb4100063\n                    \n                  .","DOI":"10.1038\/msb4100063"},{"key":"709_CR46","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1128\/AAC.05184-11","volume":"56","author":"C Welsch","year":"2012","unstructured":"Welsch, C., Schweizer, S., Shimakami, T., Domingues, F. S., Kim, S., Lemon, S. M., & Antes, I. (2012). Ketoamide resistance and hepatitis C virus fitness in Val55 variants of the NS3 serine protease. Antimicrobial Agents and Chemotherapy, \n                           56, 1907\u20131915.","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"709_CR47","doi-asserted-by":"publisher","first-page":"R16","DOI":"10.1186\/gb-2008-9-1-r16","volume":"9","author":"C Welsch","year":"2008","unstructured":"Welsch, C., Domingues, F. S., Susser, S., Antes, I., Hartmann, C., Mayr, G., et al. (2008). Molecular basis of telaprevir resistance due to V36 and T54 mutations in the NS3-4A protease of the hepatitis C virus. Genome Biology, \n                           9, R16.","journal-title":"Genome Biology"},{"key":"709_CR48","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1021\/ci300541c","volume":"53","author":"WW Xue","year":"2013","unstructured":"Xue, W. W., Jin, X. J., Ning, L. L., Wang, M. X., Liu, H. X., & Yao, X. J. (2013). Exploring the molecular mechanism of cross-resistance to HIV-1 integrase strand transfer inhibitors by molecular dynamics simulation and residue interaction network analysis. Journal of Chemical Information and Modeling, \n                           53, 210\u2013222.","journal-title":"Journal of Chemical Information and Modeling"},{"key":"709_CR49","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.tibs.2011.01.002","volume":"36","author":"NT Doncheva","year":"2011","unstructured":"Doncheva, N. T., Klein, K., Domingues, F. S., & Albrecht, M. (2011). Analyzing and visualizing residue networks of protein structures. Trends in Biochemical Sciences, \n                           36, 179\u2013182.","journal-title":"Trends in Biochemical Sciences"},{"key":"709_CR50","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1038\/nprot.2012.004","volume":"7","author":"NT Doncheva","year":"2012","unstructured":"Doncheva, N. T., Assenov, Y., Domingues, F. S., & Albrecht, M. (2012). Topological analysis and interactive visualization of biological networks and protein structures. Nature Protocols, \n                           7, 670\u2013685.","journal-title":"Nature Protocols"},{"key":"709_CR51","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1111\/cbdd.12063","volume":"81","author":"SM Ahmed","year":"2013","unstructured":"Ahmed, S. M., Kruger, H. G., Govender, T., Maguire, G. E., Sayed, Y., Ibrahim, M. A., et al. (2013). Comparison of the molecular dynamics and calculated binding free energies for nine FDA-approved HIV-1 PR drugs against subtype B and C-SA HIV PR. Chemical Biology and Drug Design, \n                           81, 208\u2013218.","journal-title":"Chemical Biology and Drug Design"},{"key":"709_CR52","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1002\/ddr.21078","volume":"74","author":"MES Soliman","year":"2013","unstructured":"Soliman, M. E. S. (2013). A hybrid structure\/pharmacophore-based virtual screening approach to design potential leads: A computer-aided design of south African HIV-1 subtype C protease inhibitors. Drug Development Research, \n                           74, 283\u2013295.","journal-title":"Drug Development Research"},{"issue":"1","key":"709_CR53","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1472-6807-8-4","volume":"8","author":"DS Kanibolotsky","year":"2008","unstructured":"Kanibolotsky, D. S., Novosyl\u2019na, O. V., Abbott, C. M., Negrutskii, B. S., & El\u2019skaya, A. V. (2008). Multiple molecular dynamics simulation of the isoforms of human translation elongation factor 1A reveals reversible fluctuations between \u201copen\u201d and \u201cclosed\u201d conformations and suggests specific for eEF1A1 affinity for Ca(2+)-calmodulin. BMC Structural Biology, \n                           8(1), 4.","journal-title":"BMC Structural Biology"},{"key":"709_CR54","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1021\/ct200909j","volume":"8","author":"AW Goetz","year":"2012","unstructured":"Goetz, A. W., Williamson, M. J., Xu, D., Poole, D., Le Grand, S., & Walker, R. C. (2012). Routine microsecond molecular dynamics simulations with AMBER on GPUs. 1. Generalized born. Journal of Chemical Theory and Computation, \n                           8, 1542\u20131555.","journal-title":"Journal of Chemical Theory and Computation"},{"key":"709_CR55","doi-asserted-by":"publisher","first-page":"3878","DOI":"10.1021\/ct400314y","volume":"9","author":"R Salomon-Ferrer","year":"2013","unstructured":"Salomon-Ferrer, R., Goetz, A. W., Poole, D., Le Grand, S., & Walker, R. C. (2013). Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle mesh Ewald. Journal of Chemical Theory and Computation, \n                           9, 3878\u20133888.","journal-title":"Journal of Chemical Theory and Computation"},{"key":"709_CR56","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1002\/wcms.1121","volume":"3","author":"R Salomon-Ferrer","year":"2013","unstructured":"Salomon-Ferrer, R., Case, D. A., & Walker., R. C. (2013). An overview of the Amber biomolecular simulation package.\u00a0WIREs Computational Molecular Science,\u00a03,\u00a0198\u2013210.","journal-title":"WIREs Computational Molecular Science"},{"key":"709_CR57","volume-title":"AMBER 12","author":"DA Case","year":"2012","unstructured":"Case, D. A., Darden, T. A., Cheatham, III, T. E., Simmerling, C. L., Wang, J., Duke, R. E., et al. (2012). AMBER 12. San Francisco: University of California."},{"key":"709_CR58","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1002\/prot.22711","volume":"78","author":"K Lindorff-Larsen","year":"2010","unstructured":"Lindorff-Larsen, K., Piana, S., Palmo, K., Maragakis, P., Klepeis, J. L., Dror, R. O., & Shaw, D. E. (2010). Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins Structure Function and Bioinformatics, \n                           78, 1950\u20131958.","journal-title":"Proteins Structure Function and Bioinformatics"},{"key":"709_CR59","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1002\/jcc.540161106","volume":"16","author":"P Cieplak","year":"1995","unstructured":"Cieplak, P., Cornell, W. D., Bayly, C., & Kollman, P. A. (1995). Application of the multimolecule and multiconformational RESP methodology to biopolymers: Charge derivation for DNA, and proteins. Journal of Computational Chemistry, \n                           16, 1357\u20131377.","journal-title":"Journal of Computational Chemistry"},{"key":"709_CR60","unstructured":"Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., et al. (2009). Gaussian 09, Revision D.01. Wallingford, CT: Gaussian, Inc."},{"key":"709_CR61","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","volume":"79","author":"WL Jorgensen","year":"1983","unstructured":"Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., & Klein, M. L. (1983). Comparison of simple potential functions for simulating liquid water. Journal of Chemical Physics, \n                           79, 926\u2013935.","journal-title":"Journal of Chemical Physics"},{"key":"709_CR62","doi-asserted-by":"publisher","first-page":"8577","DOI":"10.1063\/1.470117","volume":"103","author":"U Essmann","year":"1995","unstructured":"Essmann, U., Perera, L., Berkowitz, M. L., Darden, T., Lee, H., & Pedersen, L. G. (1995). A smooth particle mesh Ewald method. Journal of Chemical Physics, \n                           103, 8577\u20138593.","journal-title":"Journal of Chemical Physics"},{"key":"709_CR63","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","volume":"23","author":"JP Ryckaert","year":"1977","unstructured":"Ryckaert, J. P., Giovanni, C., & Berendsen, H. J. C. (1977). Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. Journal of Computational Physics, \n                           23, 327\u2013341.","journal-title":"Journal of Computational Physics"},{"key":"709_CR64","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.cpc.2012.09.022","volume":"184","author":"S Le Grand","year":"2013","unstructured":"Le Grand, S., G\u00f6tz, A. W., & Walker, R. C. (2013). SPFP: Speed without compromise\u2014A mixed precision model for GPU accelerated molecular dynamics simulations. Computer Physics Communications, \n                           184, 374\u2013380.","journal-title":"Computer Physics Communications"},{"key":"709_CR65","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.1063\/1.448118","volume":"81","author":"HJC Berendsen","year":"1984","unstructured":"Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A., & Haak, J. R. (1984). Molecular dynamics with coupling to an external bath. Journal of Chemical Physics, \n                           81, 3684\u20133690.","journal-title":"Journal of Chemical Physics"},{"key":"709_CR66","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1021\/ar000033j","volume":"33","author":"PA Kollman","year":"2000","unstructured":"Kollman, P. A., Massova, I., Reyes, C., Kuhn, B., Huo, S. H., Chong, L., et al. (2000). Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models. Accounts of Chemical Research, \n                           33, 889\u2013897.","journal-title":"Accounts of Chemical Research"},{"key":"709_CR67","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1023\/A:1008763014207","volume":"18","author":"I Massova","year":"2000","unstructured":"Massova, I., & Kollman, P. A. (2000). Combined molecular mechanical and continuum solvent approach (MM-PBSA\/GBSA) to predict ligand binding. Perspectives in Drug Discovery and Design, \n                           18, 113\u2013135.","journal-title":"Perspectives in Drug Discovery and Design"},{"key":"709_CR68","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1002\/1097-0282(2000)56:4<275::AID-BIP10024>3.0.CO;2-E","volume":"56","author":"V Tsui","year":"2000","unstructured":"Tsui, V., & Case, D. A. (2000). Theory and applications of the Generalized born solvation model in macromolecular simulations. Biopolymers, \n                           56, 275\u2013291.","journal-title":"Biopolymers"},{"key":"709_CR69","doi-asserted-by":"publisher","first-page":"3712","DOI":"10.1021\/jp994072s","volume":"104","author":"A Onufriev","year":"2000","unstructured":"Onufriev, A., Bashford, D., & Case, D. A. (2000). Modification of the generalized Born model suitable for macromolecules. Journal of Physical Chemistry B, \n                           104, 3712\u20133720.","journal-title":"Journal of Physical Chemistry B"},{"key":"709_CR70","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","volume":"14","author":"W Humphrey","year":"1996","unstructured":"Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics and Modelling, \n                           14, 33\u201338.","journal-title":"Journal of Molecular Graphics and Modelling"},{"key":"709_CR71","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1093\/bioinformatics\/btr168","volume":"27","author":"A Bakan","year":"2011","unstructured":"Bakan, A., Meireles, L. M., & Bahar, I. (2011). ProDy: Protein dynamics inferred from theory and experiments. Bioinformatics, \n                           27, 1575\u20131577.","journal-title":"Bioinformatics"},{"key":"709_CR72","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., et al. (2003). Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Research, \n                           13, 2498\u20132504.","journal-title":"Genome Research"},{"key":"709_CR73","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1016\/S0960-894X(03)00330-5","volume":"13","author":"H Choo","year":"2003","unstructured":"Choo, H., Chong, Y., & Chu, C. K. (2003). The role of 2\u2032,3\u2032-unsaturation on the antiviral activity of anti-HIV nucleosides against 3TC-resistant mutant (M184V). Bioorganic and Medicinal Chemistry Letters, \n                           13, 1993\u20131996.","journal-title":"Bioorganic and Medicinal Chemistry Letters"},{"key":"709_CR74","doi-asserted-by":"publisher","first-page":"3377","DOI":"10.1128\/AAC.47.11.3377-3383.2003","volume":"47","author":"K Diallo","year":"2003","unstructured":"Diallo, K., Gotte, M., & Wainberg, M. A. (2003). Molecular impact of the M184V mutation in human immunodeficiency virus type 1 reverse transcriptase. Antimicrobial Agents and Chemotherapy, \n                           47, 3377\u20133383.","journal-title":"Antimicrobial Agents and Chemotherapy"}],"container-title":["Cell Biochemistry and Biophysics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12013-015-0709-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12013-015-0709-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12013-015-0709-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12013-015-0709-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T18:15:34Z","timestamp":1602267334000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12013-015-0709-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,14]]},"references-count":74,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["709"],"URL":"https:\/\/doi.org\/10.1007\/s12013-015-0709-2","relation":{},"ISSN":["1085-9195","1559-0283"],"issn-type":[{"value":"1085-9195","type":"print"},{"value":"1559-0283","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,14]]},"assertion":[{"value":"14 September 2015","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no potential conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"}}]}}