Interactive chemical reactivity exploration.

Elucidating chemical reactivity in complex molecular assemblies of a few hundred atoms is, despite the remarkable progress in quantum chemistry, still a major challenge. Black-box search methods to find intermediates and transition-state structures might fail in such situations because of the high-dimensionality of the potential energy surface. Here, we propose the concept of interactive chemical reactivity exploration to effectively introduce the chemist's intuition into the search process. We employ a haptic pointer device with force feedback to allow the operator the direct manipulation of structures in three dimensions along with simultaneous perception of the quantum mechanical response upon structure modification as forces. We elaborate on the details of how such an interactive exploration should proceed and which technical difficulties need to be overcome. All reactivity-exploration concepts developed for this purpose have been implemented in the samson programming environment.

[1]  Sara Comai,et al.  A Haptic-Enhanced System for Molecular Sensing , 2009, INTERACT.

[2]  Moritz P. Haag,et al.  Real‐time quantum chemistry , 2012, 1208.3717.

[3]  Wolfgang Brandt,et al.  Virtual screening for plant PARP inhibitors – what can be learned from human PARP inhibitors? , 2012, Journal of Cheminformatics.

[4]  Martin Head-Gordon,et al.  A finite difference Davidson procedure to sidestep full ab initio hessian calculation: application to characterization of stationary points and transition state searches. , 2014, The Journal of chemical physics.

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

[6]  G. Seifert,et al.  Calculations of molecules, clusters, and solids with a simplified LCAO-DFT-LDA scheme , 1996 .

[7]  Michael Gaus,et al.  DFTB3: Extension of the self-consistent-charge density-functional tight-binding method (SCC-DFTB). , 2011, Journal of chemical theory and computation.

[8]  E. L. King,et al.  A Schematic Method of Deriving the Rate Laws for Enzyme-Catalyzed Reactions , 1956 .

[9]  J. Kussmann,et al.  Linear‐Scaling Methods in Quantum Chemistry , 2007 .

[10]  D. Black,et al.  Postulated electrocyclic reactions leading to endiandric acid and related natural products , 1980 .

[11]  Markus Reiher,et al.  A mode-selective quantum chemical method for tracking molecular vibrations applied to functionalized carbon nanotubes , 2003 .

[12]  Michael Gaus,et al.  Parameterization of DFTB3/3OB for Sulfur and Phosphorus for Chemical and Biological Applications , 2014, Journal of chemical theory and computation.

[13]  Hidde de Jong,et al.  Modeling and Simulation of Genetic Regulatory Systems: A Literature Review , 2002, J. Comput. Biol..

[14]  Markus Reiher,et al.  Haptic quantum chemistry , 2009, J. Comput. Chem..

[15]  F. A. Seiler,et al.  Numerical Recipes in C: The Art of Scientific Computing , 1989 .

[16]  Stéphane Redon,et al.  Adaptive torsion-angle quasi-statics: a general simulation method with applications to protein structure analysis and design , 2007, ISMB/ECCB.

[17]  István Mayer,et al.  Charge, bond order and valence in the AB initio SCF theory , 1983 .

[18]  Erica Harvey,et al.  Haptic representation of the atom , 2000, 2000 IEEE Conference on Information Visualization. An International Conference on Computer Visualization and Graphics.

[19]  Stéphane Redon,et al.  Block‐adaptive quantum mechanics: An adaptive divide‐and‐conquer approach to interactive quantum chemistry , 2013, J. Comput. Chem..

[20]  Markus Reiher,et al.  Generation of potential energy surfaces in high dimensions and their haptic exploration. , 2011, Chemphyschem : a European journal of chemical physics and physical chemistry.

[21]  Ralph Johnson,et al.  design patterns elements of reusable object oriented software , 2019 .

[22]  Adrian J Mulholland,et al.  Atomic Description of an Enzyme Reaction Dominated by Proton Tunneling , 2006, Science.

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

[24]  F. Weigend,et al.  Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: Design and assessment of accuracy. , 2005, Physical chemistry chemical physics : PCCP.

[25]  A. Anderson.  Electron density distribution functions and the ASED–MO theory , 1994 .

[26]  T. Frauenheim,et al.  DFTB+, a sparse matrix-based implementation of the DFTB method. , 2007, The journal of physical chemistry. A.

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

[28]  Adrian J Mulholland,et al.  Taking Ockham's razor to enzyme dynamics and catalysis. , 2012, Nature chemistry.

[29]  김삼묘,et al.  “Bioinformatics” 특집을 내면서 , 2000 .

[30]  J. C. Slater,et al.  Simplified LCAO Method for the Periodic Potential Problem , 1954 .

[31]  Markus Reiher,et al.  Convergence characteristics and efficiency of mode-tracking calculations on pre-selected molecular vibrations , 2004 .

[32]  Gotthard Seifert,et al.  Density functional tight binding , 2014, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[33]  P. Wormer,et al.  Theory and Applications of Computational Chemistry The First Forty Years , 2005 .

[34]  Nigel W. John,et al.  Chemical education using feelable molecules , 2009, Web3D '09.

[35]  J. Pople,et al.  Self‐Consistent Molecular‐Orbital Methods. I. Use of Gaussian Expansions of Slater‐Type Atomic Orbitals , 1969 .

[36]  D. Tantillo,et al.  Biosynthetic consequences of multiple sequential post-transition-state bifurcations. , 2014, Nature chemistry.

[37]  H. Eyring.  The Activated Complex in Chemical Reactions , 1935 .

[38]  G. Marin,et al.  Genesys: kinetic model construction using chemo-informatics , 2012 .

[39]  Kwang S. Kim,et al.  Theory and applications of computational chemistry : the first forty years , 2005 .

[40]  Aude Bolopion,et al.  Comparing position and force control for interactive molecular simulators with haptic feedback. , 2010, Journal of molecular graphics & modelling.

[41]  Linda J. Broadbelt,et al.  Computer Generated Pyrolysis Modeling: On-the-Fly Generation of Species, Reactions, and Rates , 1994 .

[42]  Marcus D. Hanwell,et al.  Avogadro: an advanced semantic chemical editor, visualization, and analysis platform , 2012, Journal of Cheminformatics.

[43]  Seifert,et al.  Construction of tight-binding-like potentials on the basis of density-functional theory: Application to carbon. , 1995, Physical review. B, Condensed matter.

[44]  Frederick P Brooks.  Impressions by a dinosaur - summary of Faraday discussion 169: molecular simulations and visualization. , 2014, Faraday discussions.

[45]  M. Elstner,et al.  Parametrization and Benchmark of DFTB3 for Organic Molecules. , 2013, Journal of chemical theory and computation.

[46]  M. Pilling,et al.  MESMER: an open-source master equation solver for multi-energy well reactions. , 2012, The journal of physical chemistry. A.

[47]  Sándor Suhai,et al.  Self-consistent-charge density-functional tight-binding method for simulations of complex materials properties , 1998 .

[48]  M. Reiher,et al.  Spin in density‐functional theory , 2012, 1206.2234.

[49]  Gerald R. Kneller,et al.  Superposition of molecular structures using quaternions , 1991 .

[50]  Stéphane Redon,et al.  Interactive quantum chemistry: A divide‐and‐conquer ASED‐MO method , 2012, J. Comput. Chem..

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

[52]  M. Frisch,et al.  Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields , 1994 .

[53]  Aude Bolopion,et al.  Variable gain haptic coupling for molecular simulation , 2011, 2011 IEEE World Haptics Conference.

[54]  S. Sakai.  Theoretical Analysis of Concerted and Stepwise Mechanisms of Diels−Alder Reaction between Butadiene and Ethylene , 2000 .

[55]  A. Warshel,et al.  Transition state theory can be used in studies of enzyme catalysis: lessons from simulations of tunnelling and dynamical effects in lipoxygenase and other systems , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[56]  Stéphane Redon,et al.  Interactive physically-based structural modeling of hydrocarbon systems , 2012, J. Comput. Phys..

[57]  S. Goedecker.  Linear scaling electronic structure methods , 1999 .

[58]  Pierre-Alexandre Glaude,et al.  Computer Based Generation of Reaction Mechanisms for Gas-phase Oxidation , 2000, Comput. Chem..

[59]  Stanislas Leibler,et al.  Modeling network dynamics , 2003, The Journal of cell biology.

[60]  V. Schramm,et al.  Enzymatic transition states and dynamic motion in barrier crossing. , 2009, Nature chemical biology.

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

[62]  Natal A. W. van Riel,et al.  Dynamic modelling and analysis of biochemical networks: mechanism-based models and model-based experiments , 2006, Briefings Bioinform..

[63]  Emanuel H. Rubensson,et al.  Methods for Hartree–Fock and density functional theory electronic structure calculations with linearly scaling processor time and memory usage , 2011 .

[64]  M. Head‐Gordon,et al.  A fifth-order perturbation comparison of electron correlation theories , 1989 .