Skip to main content

Advertisement

SpringerLink
Log in

Effects of the protonation state in the interaction of an HIV-1 reverse transcriptase (RT) amino acid, Lys101, and a non nucleoside RT inhibitor, GW420867X

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

Interactions between an inhibitor and amino acids from a binding pocket could help not only to understand the nature of these interactions, but also to support the design of new inhibitors. In this paper, we explore the key interaction between a second generation non-nucleoside reverse transcriptase inhibitor (NNRTI), GW420867X, and HIV-1 RT amino acid Lys101 (K101), by quantum mechanical methods. The neutral, protonated, and zwitterionic complexes of GW420867X–K101 were studied. The interaction energies were determined by SCS-MP2/def2-cc-pVQZ, and the electron density was analyzed by natural bond orbital (NBO), atoms in molecules (AIM) and reduced gradient analysis. A large increase in the interaction was observed with the tautomerization of neutral or neutral protonated species. The monomers interact by two medium-strength hydrogen bonds, one partially covalent and another noncovalent. There are some van der Waals intramolecular interactions that are topologically unstable. The nature of the intermolecular interactions was also analyzed using quantitative molecular orbital (MO) theory in combination with an energy decomposition analysis (EDA) based on dispersion-corrected density functional theory (DFT) at BLYP-D/TZ2P.

Structure (left) and gradient isosurface (right) (s = 0.05 a.u.) of the partially relaxed complex of non-nucleoside reverse transcriptase (RT) inhibitor GW420867X with neutral HIV-1 RT amino acid Lys101 (1)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2a–d
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Sharp PM, Hahn B (2011) Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med 1:1–22

    Article  Google Scholar 

  2. Piot P, Quinn TC (2013) Response to the AIDS pandemic—a global health model. N Engl J Med 368:2210–2218

    Article  CAS  Google Scholar 

  3. De Clercq EA (2011) A 40-year journey in search of selective antiviral chemotherapy. Annu Rev Pharmacol Toxicol 51:1–27

    Article  Google Scholar 

  4. Panos G, Samonis G, Alexiou VG, Kavarnou GA, Charatsis G, Falagas ME (2008) Mortality and morbidity of HIV infected patients receiving HAART: a cohort study. Curr HIV Res 6:257–260

    Article  CAS  Google Scholar 

  5. de Bethune M-P (2010) Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery, development, and use in the treatment of HIV-1 infection: a review of the last 20 years (1989–2009). Antivir Res 85:75–90

    Article  Google Scholar 

  6. Joly V, Descamps D, Yeni P (2002) NNRTI plus PI combinations in the perspective of nucleoside-sparing or nucleoside-failing antiretroviral regimens. AIDS Rev 4:128–139

    Google Scholar 

  7. Singh K, Marchand B, Rai DK, Sharma B, Michailidis E, Ryan EM, Matzek KB, Leslie MD, Hagedorn AN, Li Z, Norden PR, Hachiya A, Parniak MA, Xu H-T, Wainberg MA, Sarafianos SG (2012) Biochemical mechanism of HIV-1 resistance to rilpivirine. J Biol Chem 287:38110–38123

    Article  CAS  Google Scholar 

  8. FDA. Safety. Intelence (Etravirine). http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm180579.htm. Accessed 26 January 2014

  9. FDA. Approval of edurant (rilpivirine) a new NNRTI) for the treatment of HIV in treatment naive patients http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm256151.htm. Accessed 26 January 2014

  10. Delviks-Frankenberry KA, Nikolenko GN, Pathak VK (2010) The “connection” between HIV drug resistance and RNase H. Viruses 1476:1503

    Google Scholar 

  11. Li JZ, Paredes R, Ribaudo HJ, Svarovskaia ES, Metzner KJ, Kozal MJ, Hullsiek KH, Balduin M, Jakobsen MR, Geretti AM, Thiebaut R, Ostergaard L, Masquelier B, Johnson JA, Miller MD, Kuritzkes DR (2012) Low-frequency HIV-1 drug resistance mutations and risk of NNRTI-based antiretroviral treatment failure: a systematic review and pooled analysis. JAMA 305:1327–1335

    Article  Google Scholar 

  12. Li D, Zhan P, De Clercq E, Liu X (2012) Strategies for the design of HIV-1 non-nucleoside reverse transcriptase inhibitors: lessons from the development of seven representative paradigms. J Med Chem 55:3595–3613

    Article  CAS  Google Scholar 

  13. Das K, Martinez SE, Bauman JD, Arnold E (2012) HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism. Nat Struct Mol Biol 19:253–259

    Article  CAS  Google Scholar 

  14. Wright DW, Kashif Sadiq S, De Fabritiis G, Coveney PV (2012) Thumbs down for HIV: domain level rearrangements do occur in the NNRTI-bound HIV-1 reverse transcriptase. J Am Chem Soc 134:12885–12888

    Article  CAS  Google Scholar 

  15. Kuroda DG, Bauman JD, Challa JR, Patel D, Troxler T, Das K, Arnold E, Hochstrasser RM (2013) Snapshot of the equilibrium dynamics of a drug bound to human immunodeficiency virus 1 reverse transcriptase. Nat Chem 5:174–181

    Article  CAS  Google Scholar 

  16. Singh K, Marchand B, Rai DK, Sharma B, Michailidis E, Ryan EM, Matzek KB, Leslie MD, Hagedorn AN, Li Z, Norden PR, Hachiya A, Parniak MA, Xu H-T, Wainberg MA, Sarafianos SG (2012) Biochemical mechanism of HIV-1 resistance to rilpivirine. J Biol Chem 287:38110–38223

    Article  CAS  Google Scholar 

  17. Kroeger SMB, Rader LH, Franklin AM, Taylor EV, Smith KD, Smith RH Jr, Tirado-Rives J, Jorgensen WL (2008) Energetic effects for observed and unobserved HIV-1 reverse transcriptase mutations of residues L100, V106, and Y181 in the presence of nevirapine and efavirenz. Bioorg Med Chem Lett 18:969–972

    Article  Google Scholar 

  18. Udier-Blagovic M, Tirado-Rives J, Jorgensen WL (2004) Structural and energetic analyses of the effects of the K103N mutation of HIV-1 reverse transcriptase on efavirenz analogues. J Med Chem 47:2389–2392

    Article  CAS  Google Scholar 

  19. Kar P, Knecht V (2012) Energetics of mutation-induced changes in potency of lersivirine against HIV-1 reverse transcriptase. J Phys Chem B 116:6269–6278

    Article  CAS  Google Scholar 

  20. Saparpakorn P, Wolschann P, Karpfen A, Pungpo P, Hannongbua S (2011) Systematic investigation on the binding of GW420867X as HIV-1 reverse transcriptase inhibitor. Monatsh Chem 142:961–971, and references cited therein

    Article  CAS  Google Scholar 

  21. He X, Mei Y, Xiang Y, Zhang DW, Zhang JZH (2005) Quantum computational analysis for drug resistance of HIV-1 reverse transcriptase to nevirapine through point mutations. Proteins 61:423–432

    Article  CAS  Google Scholar 

  22. Raju RK, Burton NA, Hillier IH (2010) Modelling the binding of HIV-reverse transcriptase and nevirapine: an assessment of quantum mechanical and force field approaches and predictions of the effect of mutations on binding. Phys Chem Chem Phys 12:7117–7125

    Article  CAS  Google Scholar 

  23. Freitas RF, Galembeck SE (2006) Effect of C–H⋯S and C–H⋯Cl interactions on the conformational preference of inhibitors of TIBO family. Chem Phys Lett 423:131–137

    Article  CAS  Google Scholar 

  24. Freitas RF, Galembeck SE (2006) Computational study of the interaction between TIBO inhibitors and Y181 (C181), K101, and Y188 amino acids. J Phys Chem B 110:21287–21298

    Article  CAS  Google Scholar 

  25. Ribone SR, Leen V, Madrid M, Dehaen W, Daelemans D, Pannecouque C, Briñón MC (2012) Synthesis, biological evaluation and molecular modeling of 4,6-diarylpyrimidines and diarylbenzenes as novel non-nucleosides HIV-1 reverse transcriptase inhibitors. Eur J Med Chem 58:485–492

    Article  CAS  Google Scholar 

  26. Ren J, Nichols CE, Stamp A, Chamberlain PP, Weaver KL, Short SA, Chan JH, Kleim J-PK, Stammers DK (2007) Relationship of potency and resilience to drug resistant mutations for GW420867X revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile, Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases. J Med Chem 50:2301–2309

    Article  CAS  Google Scholar 

  27. Accelrys Software Inc. (2010) Discovery studio modeling environment, Release 3.0, San Diego: Accelrys Software Inc

  28. Schaftenaar G, Noordik JH (2000) Molden: a pre- and post-processing program for molecular and electronic structures. J Comput Aided Mol Des 14:123–134

    Article  CAS  Google Scholar 

  29. Becke AD (1997) Density-functional thermochemistry. V. Systematic optimization of exchange-correlation functionals. J Chem Phys 107:8554–8560

    Article  CAS  Google Scholar 

  30. Grimme S (2006) Semiempirical GGA-type density functional constructed with a long-range dispersion correction. J Comput Chem 27:1787–1799

    Article  CAS  Google Scholar 

  31. Weigend F, Ahlrichs R (2005) Phys Chem Chem Phys 7:3297–3305

    Article  CAS  Google Scholar 

  32. Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Accounts 120:215–241

    Article  CAS  Google Scholar 

  33. Dunning TH Jr (1989) Gaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen. J Chem Phys 90:1007–1023

    Article  CAS  Google Scholar 

  34. Distasio RA Jr, Head-Gordon M (2007) Optimized spin-component scaled second-order Møller-Plesset perturbation theory for intermolecular interaction energies. Mol Phys 105:1073–1083

    Article  CAS  Google Scholar 

  35. Boys SF, Bernardi F (1970) The calculations of small molecular interactions by the diferences of separate total energies. Some procedures with reduced errors. Mol Phys 19:553–566

    Article  CAS  Google Scholar 

  36. Gaussian 09, Revision A.02, Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski J. W, Martin R. L, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman J. B, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian, Inc., Wallingford CT

  37. Ahlrichs R, Bär M, Häser M, Horn H, Kölmel C (1989) Electronic structure calculations on workstation computers: the program system Turbomole. Chem Phys Lett 162:165–169

    Article  CAS  Google Scholar 

  38. Glendening ED, Badenhoop JK, Reed AE, Carpenter JE, Bohmann JA, Morales CM, Weinhold F (2001) NBO 5.0. Theoretical Chemistry Institute, University of Wisconsin, Madison

  39. Keith TA (2011) AIMAll (Version 11.06.19) TK Gristmill Software, Overland Park, KS (http://aim.tkgristmill.com/)

  40. Johnson ER, Keinan S, Mori-Sanchez P, Contreras-Garcia J, Cohen AJ, Yang W (2010) Revealing noncovalent interactions. J Am Chem Soc 132:6498–6506

    Article  CAS  Google Scholar 

  41. Jmol: an open-source Java viewer for chemical structures in 3D. http://www.jmol.org/

  42. Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14:33–38

    Article  CAS  Google Scholar 

  43. Youngs TGA (2010) Aten–an application for the creation, editing, and visualization of coordinates for glasses, liquids, crystals, and molecules. J Comput Chem 31:639–648

    CAS  Google Scholar 

  44. Schuchardt KL, Didier BT, Elsethagen T, Sun L, Gurumoorthi V, Chase J, Li J, Windus TL (2007) Basis set exchange: a community database for computational sciences. J Chem Inf Model 47:1045–1052

    Article  CAS  Google Scholar 

  45. te Velde G, Bickelhaupt FM, Baerends EJ, Fonseca Guerra C, van Gisbergen SJA, Snijders JG, Ziegler T (2001) Chemistry with ADF. J Comput Chem 22:931–967, See also http://www.scm.com

    Article  Google Scholar 

  46. Grimme S, Anthony J, Ehrlich S, Krieg H (2010) A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J Chem Phys 132:154104

    Article  Google Scholar 

  47. van der Wijst T, Fonseca Guerra C, Swart M, Bickelhaupt FM, Lippert B (2009) A ditopic ion-pair receptor based on stacked nucleobase quartets. Angew Chem Int Ed 48:3285–3287

    Article  Google Scholar 

  48. Fonseca Guerra C, van der Wijst T, Swart M, Poater J, Bickelhaupt FM (2010) Adenine versus guanine quartets in aqueous solution: dispersion-corrected DFT study on the differences in p-stacking and hydrogen-bonding behavior. Theor Chem Accounts 125:245–252

    Article  Google Scholar 

  49. Bickelhaupt FM, Baerends EJ (2000) Kohn-Sham density functional theory: predicting and understanding chemistry. In: Lipkowitz KB, Boyd DB (eds) Reviews in computational chemistry vol 15. Wiley-VCH, New York, pp 1–86

    Chapter  Google Scholar 

  50. Gilli P, Pretto L, Bertolasi V, Gilli G (2009) Predicting hydrogen-bond strengths from acid–base molecular properties. The pK a slide rule: toward the solution of a long-lasting problem. Acc Chem Res 42:33–44

    Article  CAS  Google Scholar 

  51. Urashima S, Asami H, Ohba M, Saigusa H (2010) Microhydration of the guanine-guanine and guanine-cytosine base pairs. J Phys Chem A 114:11231–11237

    Article  CAS  Google Scholar 

  52. Ebrahimi A, Habibi Khorassani SM, Delarami H (2009) Estimation of individual binding energies in some dimers involving multiple hydrogen bonds using topological properties of electron charge density. Chem Phys 365:18–23

    Article  CAS  Google Scholar 

  53. Poater J, Sodupe M, Bertran J, Sola M (2005) Hydrogen bonding and aromaticity in the guanine–cytosine base pair interacting with metal cations (M = Cu+, Ca2+ and Cu2+). Mol Phys 103:163–173

    Article  CAS  Google Scholar 

  54. Grimme S, Goerigk L, Fink RF (2012) Spin-component-scaled electron correlation methods. WIREs Comput Mol Sci 2:886–906

    Article  CAS  Google Scholar 

  55. Hobza P (2012) Calculations on noncovalent interactions and databases of benchmark interaction energies. Acc Chem Res 45:663–672

    Article  CAS  Google Scholar 

  56. Hohenstein EG, Sherrill CD (2012) Wavefunction methods for noncovalent interactions. WIREs Comput Mol Sci 2:304–326

    Article  CAS  Google Scholar 

  57. Riley KE, Pitonak M, Jurecka P, Hobza P (2010) Stabilization and structure calculations for noncovalent interactions in extended molecular systems based on wave function and density functional theories. Chem Rev 110:5023–5063

    Article  CAS  Google Scholar 

  58. Kozuch S, Martin JML (2013) Halogen bonds: benchmarks and theoretical analysis. J Chem Theory Comput 9:1918–1931

    Article  CAS  Google Scholar 

  59. Cerny J, Pitonak M, Riley KE, Hobza P (2011) Complete basis set extrapolation and hybrid schemes for geometry gradients of noncovalent complexes. J Chem Theory Comput 7:3924–3934

    Article  CAS  Google Scholar 

  60. Fonseca Guerra C, Bickelhaupt FM, Snijders JG, Baerends EJ (2000) Hydrogen bonding in DNA base pairs: reconciliation of theory and experiment. J Am Chem Soc 122:4117–4128

    Article  Google Scholar 

  61. Fonseca Guerra C, van der Wijst T, Bickelhaupt FM (2006) Supramolecular switches based on the guanine–cytosine (GC) Watson–Crick pair: effect of neutral and ionic substituents. Chem Eur J 12:3032–3042

    Article  Google Scholar 

  62. Fonseca Guerra C, Szekeres Z, Bickelhaupt FM (2011) Remote communication in a DNA-based nanoswitch. Chem Eur J 17:8816–8818

    Article  CAS  Google Scholar 

  63. Fonseca Guerra C, Zijlstra H, Paragi G, Bickelhaupt FM Telomere structure and stability: covalency in hydrogen bonds, not resonance assistance, causes cooperativity in guanine quartets. Chem Eur J 17:12612–12622

  64. Parreira RLT, Galembeck SE (2003) Characterization of hydrogen bonds in the interactions between the hydroperoxyl radical and organic acids. J Am Chem Soc 125:15614–15622

    Article  CAS  Google Scholar 

  65. Rauk A (1994) Orbital interaction theory of organic chemistry. Wiley, New York

    Google Scholar 

  66. Popelier PLA (2000) Atoms in molecules: an introduction. Prentice Hall, New Jersey

    Google Scholar 

  67. Bader RFW (1990) Atoms in molecules, a quantum theory. Oxford, Oxford

    Google Scholar 

  68. Bader RFW (2009) Bond paths are not chemical bonds. J Phys Chem A 113:10391–10396

    Article  CAS  Google Scholar 

  69. Matta CF, Hernandez-Trujillo J, Tang T-H, Bader RFW (2003) Hydrogen–hydrogen bonding: a stabilizing interaction in molecules and crystals. Chem Eur J 9:1940–1951

    Article  CAS  Google Scholar 

  70. Pendás AM, Francisco E, Blanco MA, Gatti C (2007) Bond paths as privileged Exchange chanels. Chem Eur J 13:9362–9371

    Article  Google Scholar 

  71. Poater J, Visser R, Solà M, Bickelhaupt FM (2007) Polycyclic benzenoids: why kinked is more stable than straight. J Org Chem 72:1134–1142

    Article  CAS  Google Scholar 

  72. Grimme S, Muck-Lichtenfeld C, Erker G, Kehr G, Wang H, Beckers H, Willner H (2009) When do interacting atoms form a chemical bond? spectroscopic measurements and theoretical analyses of dideuteriophenanthrene. Angew Chem Int Ed 48:2592–2595

    Article  CAS  Google Scholar 

  73. Cerpa E, Krapp A, Flores-Moreno R, Donald KJ, Merino G (2009) Influence of endohedral confinement on the electronic interaction between He atoms: a He2@C20H20 Case Study. Chem Eur J 15:1985–1990

    Article  CAS  Google Scholar 

  74. Cerpa E, Krapp A, Vela A, Merino G (2008) The implications of symmetry of the external potential on bond paths. Chem Eur J 14:10232–10234

    Article  CAS  Google Scholar 

  75. Poater J, Sola M, Bickelhaupt FM (2006) Hydrogen–hydrogen bonding in planar biphenyl, predicted by atoms-In-molecules theory, does not exist. Chem Eur J 12:2889–2895

    Article  CAS  Google Scholar 

  76. Strenalyuk T, Haaland A (2008) Chemical bonding in the inclusion complex of He in adamantane (He@adam): the origin of the barrier to dissociation. Chem Eur J 14:10223–10226

    Article  CAS  Google Scholar 

  77. Dem’yanov P, Polestshuk P (2012) A bond path and an attractive Ehrenfest force do not necessarily indicate bonding interactions: case study on M2X2 (M = Li, Na, K; X = H, OH, F, Cl). Chem Eur J 18:4982–4993

    Article  Google Scholar 

  78. Grabowski SJ (2011) What is the covalency of hydrogen bonding? Chem Rev 111:2597–2625

    Article  CAS  Google Scholar 

  79. Rozas I, Alkorta I, Elguero J (2000) Behavior of ylides containing N, O, and C atoms as hydrogen bond acceptors. J Am Chem Soc 122:11154–11161

    Article  CAS  Google Scholar 

  80. Ziołkowski M, Grabowski SJ, Leszczynski J (2006) Cooperativity in hydrogen-bonded interactions: ab initio and “atoms in molecules” analyses. J Phys Chem A 110:6514–6521

    Article  Google Scholar 

  81. Popelier PLA (1998) Characterization of a dihydrogen bond on the basis of the electron density. J Phys Chem A 102:1873–1878

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the Brazilian agencies CAPES/PROAP (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/Programa de Apoio à Pós-Graduação), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico; grant 481560/2010-6), and São Paulo Research Foundation (FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo) (grant 2008/02677-0) for financial support. S.E.G. thanks CNPq for a research fellowship (grant 304447/2010-2). We also thank Msc. Ali Faez Taha for technical assistance.

Author information

Authors and Affiliations

  1. Departamento de Química, FFCLRP-USP, Av. Bandeirantes, 3900, Ribeirão Preto, SP, Brazil

    Sérgio E. Galembeck

  2. Department of Theoretical Chemistry, Amsterdam Center for Multiscale Modeling (ACMM), VU University Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands

    F. Matthias Bickelhaupt & Célia Fonseca Guerra

  3. Institute of Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands

    F. Matthias Bickelhaupt

  4. Departamento de Bioquímica, IB-UNICAMP, Rua Monteiro Lobato, 255, Campinas, SP, Brazil

    Eduardo Galembeck

Authors
  1. Sérgio E. Galembeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Matthias Bickelhaupt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Célia Fonseca Guerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eduardo Galembeck
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sérgio E. Galembeck.

Additional information

This paper belongs to Topical Collection Brazilian Symposium of Theoretical Chemistry (SBQT2013)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Galembeck, S.E., Bickelhaupt, F.M., Fonseca Guerra, C. et al. Effects of the protonation state in the interaction of an HIV-1 reverse transcriptase (RT) amino acid, Lys101, and a non nucleoside RT inhibitor, GW420867X. J Mol Model 20, 2332 (2014). https://doi.org/10.1007/s00894-014-2332-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00894-014-2332-3

Keywords

Search

Navigation