Parameterization of OPLS–AA force field for the conformational analysis of macrocyclic polyketides

The parameters for the OPLS–AA potential energy function have been extended to include some functional groups that are present in macrocyclic polyketides. Existing OPLS–AA torsional parameters for alkanes, alcohols, ethers, hemiacetals, esters, and ketoamides were improved based on MP2/aug‐cc‐pVTZ and MP2/aug‐cc‐pVDZ calculations. Nonbonded parameters for the sp3 carbon and oxygen atoms were refined using Monte Carlo simulations of bulk liquids. The resulting force field predicts conformer energies and torsional barriers of alkanes, alcohols, ethers, and hemiacetals with an overall RMS deviation of 0.40 kcal/mol as compared to reference data. Densities of 19 bulk liquids are predicted with an average error of 1.1%, and heats of vaporization are reproduced within 2.4% of experimental values. The force field was used to perform conformational analysis of smaller analogs of the macrocyclic polyketide drug FK506. Structures that adopted low‐energy conformations similar to that of bound FK506 were identified. The results show that a linker of four ketide units constitutes the shortest effector domain that allows binding of the ketide drugs to FKBP proteins. It is proposed that the exact chemical makeup of the effector domain has little influence on the conformational preference of tetraketides. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 977–996, 2002

[1]  尚弘 島影.  National Institute of Standards and Technologyにおける超伝導研究及び生活 , 2001 .

[2]  William L. Jorgensen,et al.  Gas‐phase and liquid‐state properties of esters, nitriles, and nitro compounds with the OPLS‐AA force field , 2001, J. Comput. Chem..

[3]  R. Friesner,et al.  Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides† , 2001 .

[4]  William L. Jorgensen,et al.  Perfluoroalkanes: Conformational Analysis and Liquid-State Properties from ab Initio and Monte Carlo Calculations , 2001 .

[5]  J. Michl,et al.  Conformations of linear chains. Systematics and suggestions for nomenclature. , 2000, Accounts of chemical research.

[6]  P. Polavarapu,et al.  Vibrational Circular Dichroism: Predominant Conformations and Intermolecular Interactions in (R)-(-)-2-Butanol , 2000 .

[7]  B. Gold.  Neuroimmunophilin ligands: evaluation of their therapeutic potential for the treatment of neurological disorders , 2000, Expert opinion on investigational drugs.

[8]  Jinchun Xie,et al.  The O−H Stretching Δν = 3, 4, and 5 Vibrational Overtones and Conformational Study of 2-Butanol , 2000 .

[9]  Junmei Wang,et al.  How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? , 2000, J. Comput. Chem..

[10]  T. C. Bruice,et al.  α-Ketoamides and α-Ketocarbonyls: Conformational analysis and development of all-atom OPLS force field , 2000 .

[11]  D. Cremer,et al.  Molecular Geometries at Sixth Order Møller−Plesset Perturbation Theory. At What Order Does MP Theory Give Exact Geometries? , 2000 .

[12]  L. Goodman,et al.  Influence of Protonation on Internal Rotation of Dimethyl Ether , 2000 .

[13]  Y. Smeyers,et al.  Ab initio determination of the far infrared spectra of some isotopic varieties of ethanol , 2000 .

[14]  T. C. Bruice,et al.  Generation and evaluation of putative neuroregenerative drugs. Part 1: virtual point mutations to the polyketide rapamycin. , 2000, Bioorganic & medicinal chemistry.

[15]  T. C. Bruice,et al.  Generation and evaluation of putative neuroregenerative drugs. Part 2: screening virtual libraries of novel polyketides which possess the binding domain of rapamycin. , 2000, Bioorganic & medicinal chemistry.

[16]  A. K. Adya,et al.  The structure of liquid methanol by H/D substitution technique of neutron diffraction , 2000 .

[17]  W. Hehre,et al.  An ab initio molecular orbital study of the conformational energies of 2-alkyltetrahydro-2 H -pyrans (tetrahydropyrans, oxacyclohexanes, oxanes) , 2000 .

[18]  J. Blomqvist,et al.  Studies on aliphatic polyesters I: Ab initio, density functional and force field studies of esters with one carboxyl group , 1999 .

[19]  J. Lehmann,et al.  Excess molar volumes and viscosities of binary mixtures of 4-methylpyridine with methanol, ethanol, propan-1-ol, propan-2-ol, butan-2-ol, and 2-methylpropan-2-ol at 298.15 K and atmospheric pressure , 1999 .

[20]  B. Gold.  FK506 and the role of the immunophilin FKBP-52 in nerve regeneration. , 1999, Drug metabolism reviews.

[21]  H. Jiménez-Vázquez,et al.  Methyl rotational barriers in the E-forms of methyl esters , 1999 .

[22]  Arnold T. Hagler,et al.  Derivation of Class II Force Fields. 7. Nonbonded Force Field Parameters for Organic Compounds , 1999 .

[23]  D. Tozer.  The conformation and internal rotational barrier of benzyl fluoride , 1999 .

[24]  R. Bohn,et al.  Conformations of ethyl esters versus thiolesters , 1999 .

[25]  M. Matzuk,et al.  Immunophilin FK506-binding protein 52 (not FK506-binding protein 12) mediates the neurotrophic action of FK506. , 1999, The Journal of pharmacology and experimental therapeutics.

[26]  William L. Jorgensen,et al.  OPLS ALL-ATOM MODEL FOR AMINES : RESOLUTION OF THE AMINE HYDRATION PROBLEM , 1999 .

[27]  T. Halgren.  MMFF VII. Characterization of MMFF94, MMFF94s, and other widely available force fields for conformational energies and for intermolecular‐interaction energies and geometries , 1999, Journal of computational chemistry.

[28]  Andrew E. Torda,et al.  The GROMOS biomolecular simulation program package , 1999 .

[29]  W. Bailey,et al.  Conformational Studies in the Cyclohexane Series. 1. Experimental and Computational Investigation of Methyl, Ethyl, Isopropyl, and tert-Butylcyclohexanes. , 1999, The Journal of organic chemistry.

[30]  Li-Hong Xu,et al.  On the physical interpretation of torsion-rotation parameters in methanol and acetaldehyde: Comparison of global fit and ab initio results , 1999 .

[31]  J. Steiner,et al.  Immunophilins: beyond immunosuppression. , 1998, Journal of medicinal chemistry.

[32]  William L. Jorgensen,et al.  Development of an All-Atom Force Field for Heterocycles. Properties of Liquid Pyrrole, Furan, Diazoles, and Oxazoles , 1998 .

[33]  H. Motamedi,et al.  The biosynthetic gene cluster for the macrolactone ring of the immunosuppressant FK506. , 1998, European journal of biochemistry.

[34]  H. Sun,et al.  COMPASS: An ab Initio Force-Field Optimized for Condensed-Phase ApplicationsOverview with Details on Alkane and Benzene Compounds , 1998 .

[35]  J. Perchard,et al.  ROTATIONAL ISOMERISM OF ETHANOL AND MATRIX ISOLATION INFRARED SPECTROSCOPY , 1998 .

[36]  Brian J. Smith.  From Cyclohexane to 2-Hydroxy-3-oxanone: A Conformation Study , 1998 .

[37]  W. Rocha,et al.  Ab initio conformational analysis of cyclooctane molecule , 1998, J. Comput. Chem..

[38]  Alexander D. MacKerell,et al.  All-atom empirical potential for molecular modeling and dynamics studies of proteins. , 1998, The journal of physical chemistry. B.

[39]  William L. Jorgensen,et al.  Development of an all-atom force field for heterocycles. Properties of liquid pyridine and diazenes , 1998 .

[40]  William L. Jorgensen,et al.  OPLS all‐atom force field for carbohydrates , 1997 .

[41]  C. Khosla.  Harnessing the Biosynthetic Potential of Modular Polyketide Synthases. , 1997, Chemical reviews.

[42]  Leonard Katz,et al.  Manipulation of Modular Polyketide Synthases. , 1997, Chemical reviews.

[43]  Jeremy P. Scott,et al.  Polyketide library synthesis: Conformational control in extended polypropionates , 1997 .

[44]  P. Chaturvedi,et al.  A Nonimmunosuppressant FKBP-12 Ligand Increases Nerve Regeneration , 1997, Experimental Neurology.

[45]  R. Babine,et al.  MOLECULAR RECOGNITION OF PROTEIN-LIGAND COMPLEXES : APPLICATIONS TO DRUG DESIGN , 1997 .

[46]  W. Pratt,et al.  Steroid receptor interactions with heat shock protein and immunophilin chaperones. , 1997, Endocrine reviews.

[47]  Jürgen Gauss,et al.  The prediction of molecular equilibrium structures by the standard electronic wave functions , 1997 .

[48]  Justin T. Fermann,et al.  The torsional conformations of butane: Definitive energetics from ab initio methods , 1997 .

[49]  J. H. Li,et al.  Neurotrophic immunophilin ligands stimulate structural and functional recovery in neurodegenerative animal models. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[50]  William L. Jorgensen,et al.  PERFORMANCE OF THE AMBER94, MMFF94, AND OPLS-AA FORCE FIELDS FOR MODELING ORGANIC LIQUIDS , 1996 .

[51]  W. L. Jorgensen,et al.  Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids , 1996 .

[52]  E. Baulieu,et al.  Three-dimensional structure of the immunophilin-like domain of FKBP59 in solution. , 1996, Biochemistry.

[53]  S. Tsuzuki,et al.  Conformational energy profiles of n-butane, ethyl methyl ether and ethyl methyl sulfide Comparison of electron correlation correction procedures , 1996 .

[54]  K. Hall,et al.  Conformations of 1,2-Dimethoxyethane in Gas and Solution Phase from Molecular Mechanics and Monte Carlo/Stochastic Dynamics Simulations , 1996 .

[55]  J. Teixeira-Dias,et al.  CH…O intramolecular interactions determining conformational stabilities in 2-propoxyethanol , 1996 .

[56]  Jenn-Huei Lii,et al.  An improved force field (MM4) for saturated hydrocarbons , 1996, J. Comput. Chem..

[57]  Thomas A. Halgren,et al.  Merck molecular force field. IV. conformational energies and geometries for MMFF94 , 1996, J. Comput. Chem..

[58]  T. Halgren.  Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 , 1996, J. Comput. Chem..

[59]  P. Caron,et al.  X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex , 1995, Cell.

[60]  Philippe Derreumaux,et al.  A new spectroscopic molecular mechanics force field. Parameters for proteins , 1995 .

[61]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[62]  I. McLure,et al.  The orthobaric liquid and vapor densities of tetramethylsilane and of 2,2-dimethylpropane , 1993 .

[63]  L. Schäfer,et al.  Structural study and conformational analysis of t-butyl ethyl ether by gas electron diffraction, ab initio calculations and vibrational spectroscopy , 1993 .

[64]  P. Kollman,et al.  A well-behaved electrostatic potential-based method using charge restraints for deriving atomic char , 1993 .

[65]  H. Takeuchi,et al.  Inductive and steric effects on the structure of isopropyl acetate: gas electron diffraction and ab initio MO investigations , 1993 .

[66]  R F Standaert,et al.  Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex , 1991, Science.

[67]  S. Schreiber,et al.  Chemistry and biology of the immunophilins and their immunosuppressive ligands. , 1991, Science.

[68]  J. Durig,et al.  Torsional vibrations and barriers to internal rotation for ethanol and 2,2,2-trifluoroethanol , 1990 .

[69]  David A. Dixon,et al.  Ab initio conformational analysis of cyclohexane , 1990 .

[70]  Norman L. Allinger,et al.  Molecular mechanics. The MM3 force field for hydrocarbons. 1 , 1989 .

[71]  S. Schreiber,et al.  A receptor for the immuno-suppressant FK506 is a cis–trans peptidyl-prolyl isomerase , 1989, Nature.

[72]  Takao Iijima,et al.  Zero-point average structure of methanol , 1989 .

[73]  E. Herbst,et al.  The analysis of the rotational spectrum of methanol to microwave accuracy , 1989 .

[74]  Mark A. Murcko,et al.  Rotational barriers. 2. Energies of alkane rotamers. An examination of gauche interactions , 1988 .

[75]  Hiroshi Ohta,et al.  Molecular structures of tert-butyl alcohol and tert-butyl methyl ether as studied by gas electron diffraction combined with vibrational spectroscopy , 1988 .

[76]  C. Alsenoy,et al.  Structure of gaseous methyl acetate as determined by joint analysis of electron diffraction, microwave and infrared spectroscopy, supplemented by a valence force field and constraints from geometry relaxed ab initio calculations , 1986 .

[77]  P. Kollman,et al.  An approach to computing electrostatic charges for molecules , 1984 .

[78]  C. Bushweller,et al.  Stereodynamics of substituted neopentanes , 1984 .

[79]  U. Singh,et al.  A NEW FORCE FIELD FOR MOLECULAR MECHANICAL SIMULATION OF NUCLEIC ACIDS AND PROTEINS , 1984 .

[80]  Michiro Hayashi,et al.  Microwave spectrum, structure, dipole moment and internal rotation of isopropyl methyl ether , 1984 .

[81]  W. M. Haynes.  Measurements of densities and dielectric constants of liquid isobutane from 120 to 300 K at pressures to 35 MPa , 1983 .

[82]  M. Karplus,et al.  CHARMM: A program for macromolecular energy, minimization, and dynamics calculations , 1983 .

[83]  H. Günthard,et al.  Rotational isomerism in methyl formate and methyl acetate; a low-temperature matrix infrared study using thermal molecular beams , 1981 .

[84]  F. Scappini,et al.  Centrifugal Distortion and Internal Rotation Analysis in the Ground State of Trans N-Propanol , 1981 .

[85]  H. Kato,et al.  Microwave spectrum, structure, and dipole moment of the trans-trans isomer of methylpropylether , 1980 .

[86]  A. Bauder,et al.  Internal rotation of molecules with two inequivalent methyl groups: The microwave spectrum of methyl acetate , 1980 .

[87]  S. Saito,et al.  Barrier to internal rotation in ethane from the microwave spectrum of CH3CHD2 , 1979 .

[88]  Eizi Hirota,et al.  Internal rotation in isopropyl alcohol studied by microwave spectroscopy , 1979 .

[89]  J. Durig,et al.  Analysis of torsional spectra of molecules with two internal C3v rotors. X.a) Low frequency vibrational spectra, methyl torsional potential functions, and internal rotation of ethylmethylether (‐d0 and ‐d3) , 1978 .

[90]  Kazuko Oyanagi,et al.  Molecular structure and conformation of ethyl methyl sulfide as studied by gas electron diffraction. , 1978 .

[91]  Peter Groner,et al.  Analysis of torsional spectra of molecules with two internal C3v rotors. II - Far infrared and low frequency Raman spectra of dimethylether isotopes , 1977 .

[92]  J. Durig,et al.  Analysis of torsional splittings in the microwave spectra of dimethylether, CH3OCH3 and its isotopes, CD3OCH3 and CD3OCD3 , 1976 .

[93]  William F. Murphy,et al.  Rotational isomerism. XI. Raman spectra of n-butane, 2-methylbutane, and 2, 3-dimethylbutane , 1974 .

[94]  J. Perchard.  Spectres vibrationnels de basses fréquences de diverses espèces isotopiques des premiers éthers aliphatiques: II. Éthers méthyléthylique et diéthylique , 1970 .

[95]  G. E. Leroi,et al.  Infrared spectra and internal rotation in propane, isobutane and neopentane , 1969 .

[96]  James R. Hoyland,et al.  Internal Rotation in Propane: Reanalysis of the Microwave Spectrum and Quantum‐Mechanical Calculations , 1968 .

[97]  A. Birch.  Biosynthesis of polyketides and related compounds. , 1967, Science.

[98]  David R. Lide,et al.  Microwave Spectrum, Structure, and Dipole Moment of Propane , 1960 .

[99]  D. E. Mann,et al.  Microwave Spectra of Molecules Exhibiting Internal Rotation. IV. Isobutane, Tertiary Butyl Fluoride, and Trimethylphospine , 1958 .

[100]  J. Aston,et al.  The Heat Capacity and Entropy, Heats of Fusion and Vaporization, and the Vapor Pressure of Dimethyl Ether. The Density of Gaseous Dimethyl Ether , 1941 .

[101]  O. Maass,et al.  VAPOR DENSITIES AT LOW PRESSURES AND OVER AN EXTENDED TEMPERATURE RANGE. I. THE PROPERTIES OF ETHYLENE OXIDE COMPARED TO OXYGEN COMPOUNDS OF SIMILAR MOLECULAR WEIGHT , 1922 .

[102]  M. Suhm,et al.  Hydrogen Bonding in 2-Propanol. The Effect of Fluorination † , 2000 .

[103]  Ramón Bravo,et al.  Heat Capacities, Excess Enthalpies, and Volumes of Mixtures Containing Cyclic Ethers. 3. Binary Systems {Tetrahydrofuran, Tetrahydropyran, 1,4-Dioxane, or 1,3-Dioxolane + Cyclohexane or Toluene} , 1999 .

[104]  J. Durig,et al.  Enthalpy Difference between Conformers of n-Butane and the Potential Function Governing Conformational Interchange , 1995 .

[105]  S. Engelsen,et al.  The Consistent Force Field: Development of Potential Energy Functions for Conformational Analysis , 1993 .

[106]  R. G. Snyder,et al.  Experimental determination of the trans–gauche energy difference of gaseous n‐pentane and diethyl ether , 1986 .

[107]  Yoshihiro Saito,et al.  Densities, molar volumes, and cubic expansion coefficients of 78 aliphatic ethers , 1985 .

[108]  J. H. Schachtschneider,et al.  A valence force field for saturated hydrocarbons , 1965 .