skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: First principles view on chemical compound space: Gaining rigorous atomistic control of molecular properties

Journal Article · · International Journal of Quantum Chemistry
DOI:https://doi.org/10.1002/qua.24375· OSTI ID:1395172
 [1]
  1. Univ. of Basel, Basel (Switzerland); Argonne National Lab. (ANL), Argonne, IL (United States)
+ Show Author Affiliations

A well-defined notion of chemical compound space (CCS) is essential for gaining rigorous control of properties through variation of elemental composition and atomic configurations. Here, we give an introduction to an atomistic first principles perspective on CCS. First, CCS is discussed in terms of variational nuclear charges in the context of conceptual density functional and molecular grand-canonical ensemble theory. Thereafter, we revisit the notion of compound pairs, related to each other via “alchemical” interpolations involving fractional nuclear charges in the electronic Hamiltonian. We address Taylor expansions in CCS, property nonlinearity, improved predictions using reference compound pairs, and the ounce-of-gold prize challenge to linearize CCS. Finally, we turn to machine learning of analytical structure property relationships in CCS. Here, these relationships correspond to inferred, rather than derived through variational principle, solutions of the electronic Schrödinger equation.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
Argonne National Laboratory, Argonne Leadership Computing Facility; USDOE
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1395172
Journal Information:
International Journal of Quantum Chemistry, Vol. 113, Issue 12; ISSN 0020-7608
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 98 works
Citation information provided by
Web of Science

References (136)

Quantification of “fuzzy” chemical concepts: a computational perspective journal January 2012
970 Million Druglike Small Molecules for Virtual Screening in the Chemical Universe Database GDB-13 journal July 2009
Free energies of ligand binding for structurally diverse compounds journal March 2005
Two- and three-body interatomic dispersion energy contributions to binding in molecules and solids journal June 2010
Dynamically Polarizable Water Potential Based on Multipole Moments Trained by Machine Learning journal May 2009
New Method for Calculating Wave Functions in Crystals and Molecules journal October 1959
UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations journal December 1992
Molecular Electronic-Structure Theory book August 2000
An introduction to kernel-based learning algorithms journal March 2001
MOLGEN-CID A Canonizer for Molecules and Graphs Accessible through the Internet journal March 2004
Alchemical Variations of Intermolecular Energies According to Molecular Grand-Canonical Ensemble Density Functional Theory journal March 2007
Simulated annealing on free energy surfaces by a combined molecular dynamics and Monte Carlo approach journal February 1993
Higher order alchemical derivatives from coupled perturbed self-consistent field theory journal January 2012
Comment on “Fast and Accurate Modeling of Molecular Atomization Energies with Machine Learning” journal August 2012
Generalized variational density functional perturbation theory journal November 2000
Optimizing transition states via kernel-based machine learning journal May 2012
Rupp et al. Reply: journal August 2012
Ab initio molecular dynamics: Concepts, recent developments, and future trends journal May 2005
Communication: Hybrid ensembles for improved force matching journal December 2010
Predicting Crystal Structures with Data Mining of Quantum Calculations journal September 2003
High-throughput electronic band structure calculations: Challenges and tools journal August 2010
The Signature Molecular Descriptor. 1. Using Extended Valence Sequences in QSAR and QSPR Studies journal May 2003
Unified Approach for Molecular Dynamics and Density-Functional Theory journal November 1985
Robust and Affordable Multicoefficient Methods for Thermochemistry and Thermochemical Kinetics:  The MCCM/3 Suite and SAC/3 journal May 2003
Chemical Combinatorics for Alkane-Isomer Enumeration and More journal November 1998
Structure and band gaps of Ga-(V) semiconductors: The challenge of Ga pseudopotentials journal March 2008
A generalized exchange-correlation functional: the Neural-Networks approach journal May 2004
A Medicinal Chemist’s Guide to Molecular Interactions journal July 2010
Virtual screening: an endless staircase? journal April 2010
Improved a b i n i t i o effective core potentials for molecular calculations journal December 1979
Use of Pseudopotentials in Atomic‐Structure Calculations journal September 1968
Self-Consistent Equations Including Exchange and Correlation Effects journal November 1965
Identifying the minimum-energy atomic configuration on a lattice: Lamarckian twist on Darwinian evolution journal August 2008
Fast and Accurate Modeling of Molecular Atomization Energies with Machine Learning journal January 2012
The Elements of Statistical Learning book January 2009
Collective many-body van der Waals interactions in molecular systems journal August 2012
Exploring chemical space with discrete, gradient, and hybrid optimization methods journal November 2008
Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density journal January 1988
Efficient free energy calculations on small molecule host-guest systems-A combined linear interaction energy/one-step perturbation approach journal January 2009
The Effect of Structure upon the Reactions of Organic Compounds. Benzene Derivatives journal January 1937
Variational optimization of effective atom centered potentials for molecular properties journal January 2005
Towards high charge-carrier mobilities by rational design of the shape and periphery of discotics journal April 2009
Hopping Transport in Conductive Heterocyclic Oligomers:  Reorganization Energies and Substituent Effects journal February 2005
Discontinuous Nature of the Exchange-Correlation Functional in Strongly Correlated Systems journal February 2009
ReaxFF:  A Reactive Force Field for Hydrocarbons journal October 2001
Inverse molecular design in a tight-binding framework journal July 2008
Generalized Neural-Network Representation of High-Dimensional Potential-Energy Surfaces journal April 2007
Chemical space journal December 2004
Constraints on the composition of the Earth's core from ab initio calculations journal May 2000
Representing high-dimensional potential-energy surfaces for reactions at surfaces by neural networks journal September 2004
Neural network potential-energy surfaces in chemistry: a tool for large-scale simulations journal January 2011
Inverse Strategies for Molecular Design journal January 1996
Gaussian Approximation Potentials: The Accuracy of Quantum Mechanics, without the Electrons journal April 2010
Simple one-electron quantum capping potentials for use in hybrid QM/MM studies of biological molecules journal June 2002
Predictions of free energy differences from a single simulation of the initial state journal January 1994
Metallic Binding According to the Combined Approximation Procedure journal May 1936
Finding Nature’s Missing Ternary Oxide Compounds Using Machine Learning and Density Functional Theory journal June 2010
The Anticancer Drug Ellipticine Forms Covalent DNA Adducts, Mediated by Human Cytochromes P450, through Metabolism to 13-Hydroxyellipticine and Ellipticine N 2 -Oxide journal November 2004
Support vector machine regression (LS-SVM)—an alternative to artificial neural networks (ANNs) for the analysis of quantum chemistry data? journal January 2011
Ab initio molecular dynamics calculations of ion hydration free energies journal May 2009
Non‐Born–Oppenheimer density functional theory of molecular systems journal January 1982
Self-consistent band-gap corrections in density functional theory using modified pseudopotentials journal January 2007
The Number of Isomeric Hydrocarbons of the Methane Series journal August 1931
A New Approximation Method in the Problem of Many Electrons journal January 1935
Finding Density Functionals with Machine Learning journal June 2012
Computing Second-Order Functional Derivatives with Respect to the External Potential journal November 2010
Metadynamics Simulations of the High-Pressure Phases of Silicon Employing a High-Dimensional Neural Network Potential journal May 2008
Analytical evaluation of Fukui functions and real-space linear response function journal April 2012
Density-functional exchange-energy approximation with correct asymptotic behavior journal September 1988
Optimization of Effective Atom Centered Potentials for London Dispersion Forces in Density Functional Theory journal October 2004
The Fukui Potential and the Capacity of Charge and the Global Hardness of Atoms journal March 2011
Communication: Ionization potentials in the limit of large atomic number journal December 2010
A (Nearly) Universally Applicable Method for Modeling Noncovalent Interactions Using B3LYP journal June 2012
Direct computation of general chemical energy differences: Application to ionization potentials, excitation, and bond energies journal August 2006
Atom distributions in binary atom clusters: A perturbational approach and its validation in a case study journal December 2004
Homometric Structures journal June 1939
Approaches for Optimizing the First Electronic Hyperpolarizability of Conjugated Organic Molecules journal April 1991
Some Relations between Reaction Rates and Equilibrium Constants. journal August 1935
Tuning electronic eigenvalues of benzene via doping journal August 2007
Electronic structure of GaAs under strain journal November 1984
Predicting Noncovalent Interactions between Aromatic Biomolecules with London-Dispersion-Corrected DFT journal December 2007
Self-interaction-corrected pseudopotentials for silicon carbide journal May 2006
Density functionals for surface science: Exchange-correlation model development with Bayesian error estimation journal June 2012
Alchemical derivatives of reaction energetics journal August 2010
Sequence-Dependent Configurational Entropy Change of DNA upon Intercalation journal October 2010
Synthesis and biological evaluation of novel benzoxazinic analogues of ellipticine journal July 2010
Discrete Optimization of Electronic Hyperpolarizabilities in a Chemical Subspace journal November 2009
Automated Parametrization of Biomolecular Force Fields from Quantum Mechanics/Molecular Mechanics (QM/MM) Simulations through Force Matching journal January 2007
Physical Content of the Exact Kohn-Sham Orbital Energies: Band Gaps and Derivative Discontinuities journal November 1983
Atom-centered symmetry functions for constructing high-dimensional neural network potentials journal February 2011
Density‐functional thermochemistry. III. The role of exact exchange journal April 1993
Acidity constants from vertical energy gaps: density functional theory based molecular dynamics implementation journal January 2008
Conceptual Density Functional Theory journal May 2003
Accurate ab initio energy gradients in chemical compound space journal October 2009
Designing Molecules by Optimizing Potentials journal March 2006
The structures of binary compounds. I. Phenomenological structure maps journal January 1986
Forces in Molecules journal August 1939
Pseudopotentials for H to Kr optimized for gradient-corrected exchange-correlation functionals journal May 2005
Assessment of the Perdew–Burke–Ernzerhof exchange-correlation functional journal March 1999
Separable dual-space Gaussian pseudopotentials journal July 1996
Inhomogeneous Electron Gas journal November 1964
A Hamiltonian electrostatic coupling scheme for hybrid Car–Parrinello molecular dynamics simulations journal April 2002
Toward Quantitative Structure–Property Relationships for Charge Transfer Rates of Polycyclic Aromatic Hydrocarbons journal July 2011
QSAR Comparative Study of Wiener Descriptors for Weighted Molecular Graphs journal November 2000
Library of dispersion-corrected atom-centered potentials for generalized gradient approximation functionals: Elements H, C, N, O, He, Ne, Ar, and Kr journal May 2007
Molecular grand-canonical ensemble density functional theory and exploration of chemical space journal October 2006
Path Integral Computation of Quantum Free Energy Differences Due to Alchemical Transformations Involving Mass and Potential journal June 2011
Classical and quasiclassical spectral analysis of CH5+ using an ab initio potential energy surface journal November 2003
“Learn on the Fly”: A Hybrid Classical and Quantum-Mechanical Molecular Dynamics Simulation journal October 2004
Molecular Design of Porphyrin-Based Nonlinear Optical Materials journal November 2008
A simple relation between nuclear charges and potential surfaces journal May 1985
Rationale for mixing exact exchange with density functional approximations journal December 1996
Pseudopotentials that work: From H to Pu journal October 1982
Combined first-principles calculation and neural-network correction approach for heat of formation journal December 2003
A gradient-directed Monte Carlo approach to molecular design journal August 2008
Statistical Mechanics of Fluid Mixtures journal May 1935
The Number of Structural Isomers of Certain Homologs of Methane and Methanol journal July 1932
The Elements of Statistical Learning book January 2001
On representing chemical environments journal May 2013
The Elements of Statistical Learning journal August 2003
Tuning electronic eigenvalues of benzene via doping text January 2007
Molecular grand-canonical ensemble density functional theory and exploration of chemical space text January 2006
Conceptual Density Functional Theory journal July 2003
Alchemical derivatives of reaction energetics text January 2010
Ab initio molecular dynamics calculations of ion hydration free energies text January 2009
Structure and band gaps of Ga-(V) semiconductors: The challenge of Ga pseudopotentials text January 2008
Variational particle number approach for rational compound design text January 2005
Library of dispersion-corrected atom-centered potentials for generalized gradient approximation functionals: Elements H, C, N, O, He, Ne, Ar, and Kr text January 2007
Two- and three-body interatomic dispersion energy contributions to binding in molecules and solids text January 2010
Accurate ab initio energy gradients in chemical compound space text January 2009
Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density text January 1988
A gradient-directed Monte Carlo approach to molecular design text January 2008
Gaussian Approximation Potentials: the accuracy of quantum mechanics, without the electrons text January 2009
High-throughput electronic band structure calculations: challenges and tools text January 2010
Separable Dual Space Gaussian Pseudo-potentials text January 1995
Variational optimization of effective atom centered potentials for molecular properties text January 2005

Cited By (40)

Quantum Machine Learning in Chemical Compound Space journal March 2018
Study of the Chemical Space of Selected Bacteriostatic Sulfonamides from an Information Theory Point of View journal November 2016
Fourier series of atomic radial distribution functions: A molecular fingerprint for machine learning models of quantum chemical properties
  • von Lilienfeld, O. Anatole; Ramakrishnan, Raghunathan; Rupp, Matthias
  • International Journal of Quantum Chemistry, Vol. 115, Issue 16 https://doi.org/10.1002/qua.24912
journal April 2015
Crystal structure representations for machine learning models of formation energies journal April 2015
Machine learning for quantum mechanics in a nutshell journal July 2015
Exploring chemical space with alchemical derivatives: alchemical transformations of H through Ar and their ions as a proof of concept journal January 2019
Rapid and accurate molecular deprotonation energies from quantum alchemy journal January 2020
Quantum-chemistry-aided identification, synthesis and experimental validation of model systems for conformationally controlled reaction studies: separation of the conformers of 2,3-dibromobuta-1,3-diene in the gas phase journal January 2020
Simulated evolution of fluorophores for light emitting diodes journal March 2015
A fingerprint based metric for measuring similarities of crystalline structures journal January 2016
Communication: Understanding molecular representations in machine learning: The role of uniqueness and target similarity journal October 2016
Structure-based sampling and self-correcting machine learning for accurate calculations of potential energy surfaces and vibrational levels journal June 2017
Alchemical and structural distribution based representation for universal quantum machine learning journal June 2018
Machine learning model for non-equilibrium structures and energies of simple molecules journal January 2019
Chemical transferability of functional groups follows from the nearsightedness of electronic matter journal October 2017
Representing molecular and materials data for unsupervised machine learning journal April 2018
Inverse molecular design using machine learning: Generative models for matter engineering journal July 2018
Mapping and classifying molecules from a high-throughput structural database journal February 2017
Conceptual density functional theory: status, prospects, issues journal January 2020
Quantum-chemical insights from deep tensor neural networks journal January 2017
Conceptual DFT: chemistry from the linear response function journal January 2014
Operators in quantum machine learning: Response properties in chemical space journal February 2019
Machine learning of molecular electronic properties in chemical compound space journal September 2013
Quantum-chemistry-aided identification, synthesis and experimental validation of model systems for conformationally controlled reaction studies: Separation of the conformers of 2,3-dibromobuta-1,3-diene in the gas phase text January 2020
Electronic spectra from TDDFT and machine learning in chemical space text January 2015
Crystal structure representations for machine learning models of formation energies text January 2015
Fourier series of atomic radial distribution functions: A molecular fingerprint for machine learning models of quantum chemical properties text January 2015
Machine learning of molecular electronic properties in chemical compound space text January 2013
Communication: Understanding molecular representations in machine learning: The role of uniqueness and target similarity text January 2016
Rapid and accurate molecular deprotonation energies from quantum alchemy text January 2020
Accelerated materials property predictions and design using motif-based fingerprints text January 2015
Electronic Spectra from TDDFT and Machine Learning in Chemical Space text January 2015
Quantum-Chemical Insights from Deep Tensor Neural Networks text January 2016
Mapping and Classifying Molecules from a High-Throughput Structural Database preprint January 2016
Machine learning of molecular electronic properties in chemical compound space text January 2013
Big Data Meets Quantum Chemistry Approximations: The Δ-Machine Learning Approach journal April 2015
The octet rule in chemical space: Generating virtual molecules text January 2017
Alchemical normal modes unify chemical space preprint January 2018
Dictionary of 140k GDB and ZINC derived AMONs preprint January 2020
New Insights and Horizons from the Linear Response Function in Conceptual DFT book January 2019

Similar Records

Towards computational materials design from first principles using alchemical changes and derivatives.
Conference · Mon Nov 01 00:00:00 EDT 2010 · OSTI ID:1395172
Machine Learning Models Capture Plasmon Dynamics in Ag Nanoparticles
Journal Article · Thu Apr 20 00:00:00 EDT 2023 · Journal of Physical Chemistry. A, Molecules, Spectroscopy, Kinetics, Environment, and General Theory · OSTI ID:1395172
+1 more
Role of atomistic structure in the stochastic nature of conductivity in substoichiometric tantalum pentoxide
Journal Article · Mon Mar 28 00:00:00 EDT 2016 · Journal of Applied Physics · OSTI ID:1395172

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
chemical space
machine learning
density functional theory
design
alchemy