ACS Publications. Most Trusted. Most Cited. Most Read

OR SEARCH CITATIONS

My Activity
Publications
CONTENT TYPES

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Med. Chem. 1998, 41, 21, 3928-3939
RETURN TO ISSUEPREVArticleNEXT

Investigations of Neurotrophic Inhibitors of FK506 Binding Protein via Monte Carlo Simulations

View Author Information
Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107
Cite this: J. Med. Chem. 1998, 41, 21, 3928–3939
Publication Date (Web):September 19, 1998
https://doi.org/10.1021/jm980062o
Copyright © 1998 American Chemical Society
Request reuse permissions

    Article Views

    271

    Altmetric

    -

    Citations

    25
    LEARN ABOUT THESE METRICS
    Other access options
    Get e-Alerts
    Supporting Info (1)»
    SUBJECTS:

    Abstract

    The binding and solution-phase properties of six inhibitors of FK506 binding protein (FKBP12) were investigated using free energy perturbation techniques in Monte Carlo statistical mechanics simulations. These nonimmunosuppressive molecules are of current interest for their neurotrophic activity when bound to FKBP12 as well as for their potential as building blocks for chemical inducers of protein dimerization. Relative binding affinities were computed and analyzed for ligands differing by a phenyl ring, an external phenyl or pyridyl substituent, and a pipecolyl or prolyl ring. Such results are, in general, valuable for inhibitor optimization and, in the present case, bring into question some of the previously reported binding data.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    *

    In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

    Supporting Information Available

    ARTICLE SECTIONS
    Jump To

    A listing of nonbonded and torsional parameters for the FKBP12 ligands (5 pages). See any current masthead page for ordering information and Internet access instructions.

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 25 publications.

    1. Arkadiusz Maciejewski, Marta Pasenkiewicz-Gierula, Oana Cramariuc, Ilpo Vattulainen, and Tomasz Rog . Refined OPLS All-Atom Force Field for Saturated Phosphatidylcholine Bilayers at Full Hydration. The Journal of Physical Chemistry B 2014, 118 (17) , 4571-4581. https://doi.org/10.1021/jp5016627
    2. Piero Procacci, Marco Bizzarri, and Simone Marsili . Energy-Driven Undocking (EDU-HREM) in Solute Tempering Replica Exchange Simulations. Journal of Chemical Theory and Computation 2014, 10 (1) , 439-450. https://doi.org/10.1021/ct400809n
    3. Ignacio J. General and Hagai Meirovitch . Absolute Free Energy of Binding and Entropy of the FKBP12-FK506 Complex: Effects of the Force Field. Journal of Chemical Theory and Computation 2013, 9 (10) , 4609-4619. https://doi.org/10.1021/ct400484u
    4. Marco Bizzarri, Simone Marsili, and Piero Procacci . Intraligand Hydrophobic Interactions Rationalize Drug Affinities for Peptidyl−Prolyl Cis−Trans Isomerase Protein. The Journal of Physical Chemistry B 2011, 115 (19) , 6193-6201. https://doi.org/10.1021/jp110585p
    5. Lilian Olivieri and Fabrice Gardebien . Molecular Dynamics Simulations of a Binding Intermediate between FKBP12 and a High-Affinity Ligand. Journal of Chemical Theory and Computation 2011, 7 (3) , 725-741. https://doi.org/10.1021/ct100394d
    6. Modesto Orozco and, F. Javier Luque. Theoretical Methods for the Description of the Solvent Effect in Biomolecular Systems. Chemical Reviews 2000, 100 (11) , 4187-4226. https://doi.org/10.1021/cr990052a
    7. Vignesh Kumar, Joshua Jebakumar Peter, Amin Sagar, Arjun Ray, Mainak Pratim Jha, Mathieu E. Rebeaud, Satyam Tiwari, Pierre Goloubinoff, Fnu Ashish, Koyeli Mapa. Interdomain communication suppressing high intrinsic ATP ase activity of Sse1 is essential for its co‐disaggregase activity with Ssa1. The FEBS Journal 2020, 287 (4) , 671-694. https://doi.org/10.1111/febs.15045
    8. Lilian Olivieri, Fabrice Gardebien, . Structure-Affinity Properties of a High-Affinity Ligand of FKBP12 Studied by Molecular Simulations of a Binding Intermediate. PLoS ONE 2014, 9 (12) , e114610. https://doi.org/10.1371/journal.pone.0114610
    9. Yvonne Westermaier, Roderick E. Hubbard. Free Energy Methods in Ligand Design. 2013, 373-415. https://doi.org/10.1002/9783527677016.ch16
    10. Michael R. Shirts, David L. Mobley, John D. Chodera. Chapter 4 Alchemical Free Energy Calculations: Ready for Prime Time?. 2007, 41-59. https://doi.org/10.1016/S1574-1400(07)03004-6
    11. Yong Xu, Renxiao Wang. A computational analysis of the binding affinities of FKBP12 inhibitors using the MM‐PB/SA method. Proteins: Structure, Function, and Bioinformatics 2006, 64 (4) , 1058-1068. https://doi.org/10.1002/prot.21044
    12. Guha Jayachandran, Michael R. Shirts, Sanghyun Park, Vijay S. Pande. Parallelized-over-parts computation of absolute binding free energy with docking and molecular dynamics. The Journal of Chemical Physics 2006, 125 (8) https://doi.org/10.1063/1.2221680
    13. William L. Jorgensen, Julian Tirado–Rives. Molecular modeling of organic and biomolecular systems using BOSS and MCPRO. Journal of Computational Chemistry 2005, 26 (16) , 1689-1700. https://doi.org/10.1002/jcc.20297
    14. Martin Leitgeb, Christian Schröder, Stefan Boresch. Alchemical free energy calculations and multiple conformational substates. The Journal of Chemical Physics 2005, 122 (8) https://doi.org/10.1063/1.1850900
    15. Allan Wissner, Philip R. Hamann, Ramaswamy Nilakantan, Lee M. Greenberger, Fei Ye, Timothy A. Rapuano, Frank Loganzo. Syntheses and EGFR kinase inhibitory activity of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitriles. Bioorganic & Medicinal Chemistry Letters 2004, 14 (6) , 1411-1416. https://doi.org/10.1016/j.bmcl.2004.01.034
    16. Marilyn Smith, Sandra Ruby, Stanislav Horouzhenko, Bryan Buckingham, Julia Richardson, Ina Puleri, Emily Potts, William Jorgensen, Edward Arnold, Wanyi Zhang, Stephen Hughes, Christopher Michejda, Richard Smith. HIV-1 Reverse Transcriptase Variants: Molecular Modeling of Y181C, V106A, L100I, and K103N Mutations with Nonnucleoside Inhibitors Using Monte Carlo Simulations in Combination with a Linear Response Method. Drug Design and Discovery 2003, 18 (4) , 151-163. https://doi.org/10.3109/10559610390484203
    17. Alea A. Mills. Changing colors in mice: an inducible system that delivers: Figure 1.. Genes & Development 2001, 15 (12) , 1461-1467. https://doi.org/10.1101/gad.909301
    18. Christian Sich, Sabina Improta, David John Cowley, Chantal Guenet, Jean‐Pierre Merly, Michael Teufel, Vladimir Saudek. Solution structure of a neurotrophic ligand bound to FKBP12 and its effects on protein dynamics. European Journal of Biochemistry 2000, 267 (17) , 5342-5355. https://doi.org/10.1046/j.1432-1327.2000.01551.x
    19. Kalju Kahn, Thomas C. Bruice. α-Ketoamides and α-Ketocarbonyls: Conformational analysis and development of all-atom OPLS force field. Bioorganic & Medicinal Chemistry 2000, 8 (8) , 1881-1891. https://doi.org/10.1016/S0968-0896(00)00122-X
    20. Marilyn B.Kroeger Smith, Michelle L. Lamb, Julian Tirado-Rives, William L. Jorgensen, Christopher J. Michejda, Sandra K. Ruby, Richard H. Smith. Monte Carlo calculations on HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor 8-Cl TIBO: contribution of the L100I and Y181C variants to protein stability and biological activity. Protein Engineering, Design and Selection 2000, 13 (6) , 413-421. https://doi.org/10.1093/protein/13.6.413
    21. Cordelia Schiene, Gunter Fischer. Enzymes that catalyse the restructuring of proteins. Current Opinion in Structural Biology 2000, 10 (1) , 40-45. https://doi.org/10.1016/S0959-440X(99)00046-9
    22. Gregory S. Hamilton, Christine Thomas. Immunophilins. 2000, 1-84. https://doi.org/10.1016/S1067-5698(00)80003-6
    23. M. Rami Reddy, Mark D. Erion, Atul Agarwal. Free Energy Calculations: Use and Limitations in Predicting Ligand Binding Affinities. 2000, 217-304. https://doi.org/10.1002/9780470125939.ch4
    24. Yimin Qian, Juan Jose Marugan, Renae D. Fossum, Andreas Vogt, Said M. Sebti, Andrew D. Hamilton. Probing the hydrophobic pocket of farnesyltransferase: aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors. Bioorganic & Medicinal Chemistry 1999, 7 (12) , 3011-3024. https://doi.org/10.1016/S0968-0896(99)00252-7
    25. Michelle L. Lamb, Julian Tirado-Rives, William L. Jorgensen. Estimation of the binding affinities of FKBP12 inhibitors using a linear response method. Bioorganic & Medicinal Chemistry 1999, 7 (5) , 851-860. https://doi.org/10.1016/S0968-0896(99)00015-2
    Download PDF

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect