Conformational analysis of arginine in gas phase—A strategy for scanning the potential energy surface effectively

The determination of all possible low‐lying energy conformers of flexible molecules is of fundamental interest for various applications. It necessitates a reliable conformational search that is able to detect all important minimum structures and calculates the energies on an adequate level of theory. This work presents a strategy to identify low‐energy conformers using arginine as an example by means of a force‐field based conformational search in combination with high‐level geometry optimizations (RI‐MP2/TZVPP+). The methods used for various stages in the conformational search strategy are shown and various pitfalls are discussed. We can show that electronic energies calculated on a DFT level of theory with standard exchange‐correlation functionals strongly underestimate the intramolecular stabilization resulting from stacked orientations of the guanidine and carbonyl moiety of arginine due to the deficiency of DFT to describe dispersion effects. In this case by usage of electron correlation methods, low energy conformers comprising stacked arrangements that are counterintuitive become favorable. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

[1]  Bernd Engels,et al.  Difficulties in the calculation of electron spin resonance parameters using density functional methods , 1994 .

[2]  J. B. Paul,et al.  IS ARGININE ZWITTERIONIC OR NEUTRAL IN THE GAS PHASE? RESULTS FROM IR CAVITY RINGDOWN SPECTROSCOPY , 1998 .

[3]  B. Engels,et al.  An experimental and computational study on the reactivity and regioselectivity for the nitrosoarene ene reaction: comparison with triazolinedione and singlet oxygen. , 2001, Journal of the American Chemical Society.

[4]  F. Weigend.  Accurate Coulomb-fitting basis sets for H to Rn. , 2006, Physical chemistry chemical physics : PCCP.

[5]  Michael T. Bowers,et al.  On the Stability of Amino Acid Zwitterions in the Gas Phase: The Influence of Derivatization, Proton Affinity, and Alkali Ion Addition , 2000 .

[6]  P. Strevens.  Iii , 1985 .

[7]  Martin F. Jarrold,et al.  Gas-Phase Zwitterions in the Absence of a Net Charge , 2004 .

[8]  Filipp Furche,et al.  Nuclear second analytical derivative calculations using auxiliary basis set expansions , 2004 .

[9]  Peter S. Shenkin,et al.  Cluster analysis of molecular conformations , 1994, J. Comput. Chem..

[10]  Walter Thiel,et al.  The Importance of the Active Site Histidine for the Activity of Epoxide‐ or Aziridine‐Based Inhibitors of Cysteine Proteases , 2007, ChemMedChem.

[11]  Christof Hättig,et al.  Optimization of auxiliary basis sets for RI-MP2 and RI-CC2 calculations: Core–valence and quintuple-ζ basis sets for H to Ar and QZVPP basis sets for Li to Kr , 2005 .

[12]  Sebastian Schlund,et al.  "Knock-out" analogues as a tool to quantify supramolecular processes: a theoretical study of molecular interactions in guanidiniocarbonyl pyrrole carboxylate dimers. , 2005, Journal of the American Chemical Society.

[13]  Piotr Skurski,et al.  Non-ionic and zwitterionic forms of neutral arginine – an ab initio study , 2001 .

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

[15]  Reinhart Ahlrichs,et al.  Semidirect MP2 gradient evaluation on workstation computers: The MPGRAD program , 1993, J. Comput. Chem..

[16]  E. Anslyn,et al.  Anion recognition: synthetic receptors for anions and their application in sensors. , 1999, Current opinion in chemical biology.

[17]  Z. Maksić,et al.  Neutral vs. zwitterionic form of arginine—an ab initio study , 1999 .

[18]  E. Williams,et al.  Structures of protonated arginine dimer and bradykinin investigated by density functional theory: further support for stable gas-phase salt bridges. , 2000, The journal of physical chemistry. A.

[19]  Holger Patzelt,et al.  RI-MP2: optimized auxiliary basis sets and demonstration of efficiency , 1998 .

[20]  Marco Häser,et al.  Improvements on the direct SCF method , 1989 .

[21]  Bernd Engels,et al.  Theoretical studies about the influence of different ring substituents on the nucleophilic ring opening of three-membered heterocycles and possible implications for the mechanisms of cysteine protease inhibitors. , 2005, The Journal of organic chemistry.

[22]  Philip A. Gale.  Anion and ion-pair receptor chemistry: highlights from 2000 and 2001 , 2003 .

[23]  Eric V. Anslyn,et al.  Abiotic guanidinium containing receptors for anionic species , 2003 .

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

[25]  Filipp Furche,et al.  An efficient implementation of second analytical derivatives for density functional methods , 2002 .

[26]  Bernd Engels,et al.  Computational assessment of the electronic structures of cyclohexa-1,2,4-triene, 1-oxacyclohexa-2,3,5-triene (3delta(2)-pyran), their benzo derivatives, and cyclohexa-1,2-diene. An experimental approach to 3delta(2)-pyran. , 2002, Journal of the American Chemical Society.

[27]  Bernd Engels,et al.  Model Calculations about the Influence of Protic Environments on the Alkylation Step of Epoxide, Aziridine, and Thiirane Based Cysteine Protease Inhibitors , 2004 .

[28]  Richard J. Fitzmaurice,et al.  Synthetic receptors for carboxylic acids and carboxylates , 2002 .

[29]  Thomas Schrader,et al.  Functional Synthetic Receptors , 2005 .

[30]  A. Becke.  Density-functional thermochemistry. V. Systematic optimization of exchange-correlation functionals , 1997 .

[31]  Bernd Engels,et al.  Theoretical study of electron spin resonance parameters: H2CN and H2CO+ , 1994 .

[32]  A. Schäfer,et al.  Fully optimized contracted Gaussian basis sets of triple zeta valence quality for atoms Li to Kr , 1994 .

[33]  Angela K. Wilson,et al.  Gaussian basis sets for use in correlated molecular calculations. VI. Sextuple zeta correlation consistent basis sets for boron through neon , 1996 .

[34]  F. Schmidtchen,et al.  Artificial Organic Host Molecules for Anions. , 1997, Chemical reviews.

[35]  Wolfgang Lindner,et al.  Noncovalent binding between guanidinium and anionic groups: focus on biological- and synthetic-based arginine/guanidinium interactions with phosph[on]ate and sulf[on]ate residues. , 2005, Chemical reviews.

[36]  Bernd Engels,et al.  A combined computational and experimental study of the hydrogen-bonded dimers of xanthine and hypoxanthine. , 2005, The journal of physical chemistry. A.

[37]  Antonio Bianchi,et al.  Supramolecular chemistry of anions , 1997 .

[38]  Marco Häser,et al.  Auxiliary basis sets to approximate Coulomb potentials (Chem. Phys. Letters 240 (1995) 283-290) , 1995 .

[39]  P. Beer,et al.  Molecular recognition of anions by synthetic receptors. , 1997, Current opinion in chemical biology.

[40]  J. Simons,et al.  Low-energy tautomers and conformers of neutral and protonated arginine. , 2001, Journal of the American Chemical Society.

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

[42]  R. A. Jockusch,et al.  Structure of cationized arginine (arg.m, m = h, li, na, k, rb, and cs) in the gas phase: further evidence for zwitterionic arginine. , 1999, The journal of physical chemistry. A.

[43]  Emelyn Smith,et al.  A comparison of the Low Mode and Monte Carlo conformational search methods. , 2002, Journal of molecular graphics & modelling.

[44]  Rick L. Ornstein,et al.  What Happens to Salt-Bridges in Nonaqueous Environments: Insights from Quantum Mechanics Calculations , 1996 .

[45]  T. H. Dunning.  Gaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen , 1989 .

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

[47]  Hans W. Horn,et al.  ELECTRONIC STRUCTURE CALCULATIONS ON WORKSTATION COMPUTERS: THE PROGRAM SYSTEM TURBOMOLE , 1989 .

[48]  István Kolossváry,et al.  Low‐mode conformational search elucidated: Application to C39H80 and flexible docking of 9‐deazaguanine inhibitors into PNP , 1999 .

[49]  Bernd Engels,et al.  Study of influences of various excitation classes onab initio calculated isotropic hyperfine coupling constants , 1993 .

[50]  J. Pople,et al.  Self-consistent molecular orbital methods. 21. Small split-valence basis sets for first-row elements , 2002 .

[51]  W. Clark Still,et al.  An unbounded systematic search of conformational space , 1991 .

[52]  William A. Goddard,et al.  Cooperative Salt Bridge Stabilization of Gas-Phase Zwitterions in Neutral Arginine Clusters , 2002 .

[53]  R. Ahlrichs,et al.  Efficient molecular numerical integration schemes , 1995 .

[54]  Sebastian Schlund,et al.  Geometry and cooperativity effects in adenosine-carboxylic acid complexes. , 2005, Journal of the American Chemical Society.

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

[56]  R. Ahlrichs,et al.  Geometry optimization in generalized natural internal coordinates , 1999 .

[57]  James E. Huheey,et al.  Inorganic chemistry; principles of structure and reactivity , 1972 .

[58]  Donald B. Boyd,et al.  Evaluation of Computational Chemistry Methods: Crystallographic and Cheminformatics Analysis of Aminothiazole Methoximes , 2005, J. Chem. Inf. Model..

[59]  Filipp Furche,et al.  Efficient characterization of stationary points on potential energy surfaces , 2002 .

[60]  F. Weigend,et al.  RI-MP2: first derivatives and global consistency , 1997 .

[61]  Christian Seel,et al.  Molecular recognition of organic acids and anions — Receptor models for carboxylates, amino acids, and nucleotides , 1995 .

[62]  G. Chang,et al.  An internal-coordinate Monte Carlo method for searching conformational space , 1989 .