Machine learning predictions of molecular properties: Accurate many-body potentials and nonlocality in chemical space

in Journal of Physical Chemistry Letters (2015), 6(12), 2326-2331

Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical ... [more ▼]

Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstrate prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the "holy grail" of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. In addition, the same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies. © 2015 American Chemical Society. [less ▲]

Collective many-body van der Waals interactions in molecular systems

in Proceedings of the National Academy of Sciences of the United States of America (2012), 109(37), 14791-14795

Van der Waals (vdW) interactions are ubiquitous in molecules and condensed matter, and play a crucial role in determining the structure, stability, and function for a wide variety of systems. The accurate ... [more ▼]

Van der Waals (vdW) interactions are ubiquitous in molecules and condensed matter, and play a crucial role in determining the structure, stability, and function for a wide variety of systems. The accurate prediction of these interactions from first principles is a substantial challenge because they are inherently quantum mechanical phenomena that arise from correlations between many electrons within a given molecular system. We introduce an efficient method that accurately describes the nonadditive many-body vdW energy contributions arising from interactions that cannot be modeled by an effective pairwise approach, and demonstrate that such contributions can significantly exceed the energy of thermal fluctuations - a critical accuracy threshold highly coveted during molecular simulations - in the prediction of several relevant properties. Cases studied include the binding affinity of ellipticine, a DNA-intercalating anticancer agent, the relative energetics between the A- and B-conformations of DNA, and the thermodynamic stability among competing paracetamol molecular crystal polymorphs. Our findings suggest that inclusion of the many-body vdW energy is essential for achieving chemical accuracy and therefore must be accounted for in molecular simulations. [less ▲]