Quantum Mechanical Energy-Based Screening of Combinatorially Generated Library of Tautomers. TauTGen: A Tautomer Generator Program

We describe a procedure of finding low-energy tautomers of a molecule. The procedure consists of (i) combinatorial generation of a library of tautomers, (ii) screening based on the results of geometry optimization of initial structures performed at the density functional level of theory, and (iii) final refinement of geometry for the top hits at the second-order Möller-Plesset level of theory followed by single-point energy calculations at the coupled cluster level of theory with single, double, and perturbative triple excitations. The library of initial structures of various tautomers is generated with TauTGen, a tautomer generator program. The procedure proved to be successful for these molecular systems for which common chemical knowledge had not been sufficient to predict the most stable structures.

[1]  Maciej Haranczyk,et al.  Excess electron attachment induces barrier-free proton transfer in binary complexes of uracil with H2Se and H2S but not with H2O , 2003 .

[2]  B. Tidor.  Molecular dynamics simulations , 1997, Current Biology.

[3]  Maciej Gutowski,et al.  Stabilization of very rare tautomers of 1-methylcytosine by an excess electron. , 2005, The journal of physical chemistry. A.

[4]  Zhongli Cai,et al.  DFT Calculations of the Electron Affinities of Nucleic Acid Bases: Dealing with Negative Electron Affinities , 2002 .

[5]  G. Schaftenaar,et al.  Molden: a pre- and post-processing program for molecular and electronic structures* , 2000, J. Comput. Aided Mol. Des..

[6]  William L. Jorgensen,et al.  Energy profile for a nonconcerted SN2 reaction in solution , 1985 .

[7]  Hans-Joachim Werner,et al.  Coupled cluster theory for high spin, open shell reference wave functions , 1993 .

[8]  B. Hay,et al.  HostDesigner: a program for the de novo structure-based design of molecular receptors with binding sites that complement metal ion guests. , 2002, Inorganic chemistry.

[9]  J. Rak,et al.  Barrier-free intermolecular proton transfer in the uracil-glycine complex induced by excess electron attachment , 2002 .

[10]  T. Dunning,et al.  Electron affinities of the first‐row atoms revisited. Systematic basis sets and wave functions , 1992 .

[11]  H. Berendsen,et al.  COMPUTER-SIMULATION OF MOLECULAR-DYNAMICS - METHODOLOGY, APPLICATIONS, AND PERSPECTIVES IN CHEMISTRY , 1990 .

[12]  David E. Bernholdt,et al.  High performance computational chemistry: An overview of NWChem a distributed parallel application , 2000 .

[13]  Per-Olov Löwdin,et al.  Proton Tunneling in DNA and its Biological Implications , 1963 .

[14]  J. H. Hendricks,et al.  Dipole bound, nucleic acid base anions studied via negative ion photoelectron spectroscopy , 1996 .

[15]  A. Becke.  Density-functional thermochemistry. III. The role of exact exchange , 1993 .

[16]  G. Fogarasi,et al.  Relative Stabilities of Three Low-Energy Tautomers of Cytosine: A Coupled Cluster Electron Correlation Study , 2002 .

[17]  A. Hagler,et al.  Chemoinformatics and Drug Discovery , 2002, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry.

[18]  Peter J. Knowles,et al.  Perturbative corrections to account for triple excitations in closed and open shell coupled cluster theories , 1994 .

[19]  Tomasz Puzyn,et al.  Computational estimation of logarithm of n-octanol/air partition coefficient and subcooled vapor pressures of 75 chloronaphthalene congeners , 2005 .

[20]  B. Roos,et al.  Lecture notes in quantum chemistry , 1992 .

[21]  L. Paglieri,et al.  A Density Functional Study of Tautomerism of Uracil and Cytosine , 1994 .

[22]  M. Prueitt.  Computer Simulation of Molecular Dynamics. , 1971 .

[23]  M Karplus,et al.  The meaning of component analysis: decomposition of the free energy in terms of specific interactions. , 1995, Journal of molecular biology.

[24]  W. L. Jorgensen.  The Many Roles of Computation in Drug Discovery , 2004, Science.

[25]  Arieh Warshel,et al.  Langevin Dipoles Model for ab Initio Calculations of Chemical Processes in Solution: Parametrization and Application to Hydration Free Energies of Neutral and Ionic Solutes and Conformational Analysis in Aqueous Solution , 1997 .

[26]  Simone Morpurgo,et al.  Ab initio study of intramolecular proton transfer reactions in cytosine , 1997 .

[27]  Maciej Gutowski,et al.  Stabilization of very rare tautomers of uracil by an excess electron. , 2005, Physical chemistry chemical physics : PCCP.

[28]  A. Becke,et al.  Density-functional exchange-energy approximation with correct asymptotic behavior. , 1988, Physical review. A, General physics.

[29]  Parr,et al.  Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. , 1988, Physical review. B, Condensed matter.

[30]  Maciej Gutowski,et al.  Finding adiabatically bound anions of guanine through a combinatorial computational approach. , 2005, Angewandte Chemie.

[31]  Gerd Folkers,et al.  Tautomerism in Computer‐Aided Drug Design , 2003, Journal of receptor and signal transduction research.

[32]  Jacopo Tomasi,et al.  Molecular Interactions in Solution: An Overview of Methods Based on Continuous Distributions of the Solvent , 1994 .

[33]  Arieh Warshel,et al.  Computer Modeling of Chemical Reactions in Enzymes and Solutions , 1991 .

[34]  Kamil Mazurkiewicz,et al.  On the unusual stability of valence anions of thymine based on very rare tautomers: A computational study. , 2006, The journal of physical chemistry. B.