142. Infrared signatures of isomer selectivity and symmetry breaking in the Cs+(H2O)3 complex using many-body
potential energy functions. M. Riera, J.J. Talbot, R.P. Steele, F. Paesani. J. Chem. Phys. 153, 044306 (2020).
A quantitative description of the interactions between ions and water is key to characterizing the role played
by ions in mediating fundamental processes that take place in aqueous environments. At the molecular level,
vibrational spectroscopy provides a unique means to probe the multidimensional potential energy surface of
small ion−water clusters. In this study, we combine the MB-nrg potential energy functions recently developed
for ion−water interactions with perturbative corrections to vibrational self-consistent field theory and the
local-monomer approximation to disentangle many-body effects on the stability and vibrational structure
of the Cs+(H2O)3 cluster. Since several low-energy, thermodynamically accessible isomers exist for
Cs+(H2O)3, even small changes in the description of the underlying potential energy surface can result in
large differences in the relative stability of the various isomers. Our analysis demonstrates that a quantitative
account for three-body energies and explicit treatment of cross-monomer vibrational couplings are required
to reproduce the experimental spectrum.
© Paesani Research Group. All rights reserved.
137. Modeling spontaneous charge transfer at metal/organic hybrid heterostructures. V.O. Özçelik, Y. Li, W. Xiong,
F. Paesani. J. Phys. Chem. C 124, 4802 (2020).
Using various metal/poly(3- hexylthiophene)(P3HT) heterostructure models, we reveal that the level of
spontaneous charge transfer and electronic coupling at these interfaces depend on the conformational
regularity of the organic polymer deposited on the metal substrate. Using ab-initio quantum chemical
calculations based on density functional theory (DFT) and heterodyne vibrational sum frequency
generation (HD-VSFG) measurements, we show that inducing regio-randomness into the organic polymer
mod- ifies the intensity of interfacial electronic states, level of hybridization, density of interfacial charge
transfer and the electronic wave function of the material. We present the HD-VSFG responses of the
metal/P3HT heterojunctions containing both regio-regular and regio-random P3HT structures and show
that the amount of non-resonant signal is closely related to the level of the spontaneous charge transfer
at the interface. Thus, by measuring the non-resonant response of the metal/P3HT heterojunctions,
the level of spontaneous charge transfer at the interface can be determined.
138. Computer simulations explain mutation-induced structural and functional effects on the DNA editing
efficiency of adenosine base editors. K.L. Rallapalli, A.C. Komor, F. Paesani. Sci. Adv. 6, eaaz2309 (2020).
Adenine base editors (ABEs), facilitate the efficient modification of A:T base pairs to G⋮C at targeted genomic
loci via the deamination of adenine to inosine. ABEs were developed by engineering and evolving a tRNA
adenosine deaminase enzyme (TadA) into a single-stranded DNA (ssDNA) editing enzyme. A mechanistic
understanding of the contributions of the individual mutations to ssDNA editing efficiency of ABEs remains
unknown. Here, we use MD simulations to explore the structural and functional role played by the initial
mutations in the onset of ssDNA modifying activity of the TadA enzyme. Atomistic insights into the system
reveal that these early mutations lead to intricate conformational changes in the structure of the protein.
In particular, the first mutation, Asp108Asn, is associated with an enhancement in the binding free energy
of the TadA* to ssDNA. Simulations and experimental reversion analyses verify the importance of this single
mutation in imparting functional promiscuity to the TadA enzyme and suggest that the enzyme performs
base editing as a monomer rather than a dimer.
139. Data-driven many-body models for molecular fluids: CO2/H2O mixtures as a case study. M. Riera, E.P. Yeh,
F. Paesani. J. Chem. Theory Comput. 16, 2246 (2020).
In this study, we extend the scope of the many-body TTM-nrg and MB-nrg potential energy functions (PEFs),
originally introduced for halide ion–water and alkali-metal ion–water interactions, to the modeling of carbon
dioxide and water mixtures as prototypical examples of molecular fluids. Both TTM-nrg and MB-nrg PEFs
are derived entirely from electronic structure data obtained at the coupled cluster level of theory and are,
by construction, compatible with MB-pol, a many-body PEF that has been shown to accurately reproduce
the properties of water. By providing a physically correct description of many-body effects at both short and
long ranges, the MB-nrg PEFs are shown to quantitatively represent the global potential energy surfaces
of the CO2–CO2 and CO2–H2O dimers and the energetics of small clusters as well as to correctly reproduce
various properties in both gas and liquid phases. Building upon previous studies of aqueous systems, our
analysis provides further evidence for the accuracy and efficiency of the MB-nrg framework in representing
molecular interactions in fluid mixtures at different thermodynamic conditions.
140. Active learning of many-body configuration space: Application to the Cs+–water MB-nrg potential energy
function as a case study. Y. Zhai, A. Caruso, S. Gao, F. Paesani. J. Chem. Phys. 152, 144103 (2020).
The efficient selection of representative configurations that are used in high-level electronic structure
calculations needed for the development of many-body molecular models poses a challenge to current
data-driven approaches to molecular simulations. Here, we introduce an active learning (AL) framework
for generating training sets corresponding to individual many-body contributions to the energy of a
N-body system, which are required for the development of MB-nrg potential energy functions (PEFs).
Our AL framework is based on uncertainty and error estimation, and uses Gaussian process regression
to identify the most relevant configurations that are needed for an accurate representation of the energy
landscape of the molecular system under exam. Considering the computational cost associated with
high-level electronic structure calculations for training set configurations, our AL framework is particularly
well-suited to the development of many-body PEFs, with chemical and spectroscopic accuracy, for
molecular simulations from the gas to condensed phase.
141. On the nature of alkali ion−water interactions: Insights from many-body representations and density
functional theory. II. C.K. Egan, B.B. Bizzarro, M. Riera, F. Paesani. J. Chem. Theory Comput. 16, 3055 (2020).
Interaction energies of alkali ion−water dimers, M+(H2O), and trimers, M+(H2O)2, with M = Li, Na, K, Rb,
Cs, are investigated using various many-body potential en- ergy functions, and exchange correlation
functionals selected across the hierarchy of density functional theory approximations. Analysis of
interaction energy decomposi- tions indicates that close range interactions such as Pauli repulsion,
charge transfer, and charge penetration must be captured in order to reproduce accurate interaction
energies. In particular, it is found that simple classical polarizable models must be supplemented with
dedicated terms which account for these close range interactions in order to achieve chemical
accuracy across configuration space. It is also found that the XC functionals mostly differ from each
other in their Pauli repulsion + dispersion energies, and hence benefit from the inclusion of nonlocal
terms such as Hartree-Fock exchange and dependence on the electronic kinetic energy density in
order to reproduce the interactions that contribute to this term, namely Pauli repulsion and dispersion.
143. How good are polarizable and flexible models for water: Insights from a many-body perspective.
E. Lambros, F. Paesani. J. Chem. Phys. 153, 060901 (2020).
We present a systematic analysis of state-of-the-art polarizable water models from a many-body
perspective, with a specific focus on their ability to represent the Born-Oppenheimer potential energy
surface of water from the gas to the liquid phase. Using coupled cluster data in the completed basis
set limit as a reference, we examine the accuracy of the polarizable models in reproducing many-body
contributions to interaction energies and harmonic frequencies of water clusters and compare their
performance with that of MB-pol, an explicit many-body model that has been shown to correctly
predict the properties of water across the entire phase diagram. We find that, while they are able to
reproduce the energetics of minimum-energy structures, the polarizable models examined here suffer
from inadequate representations of many-body effects for distorted configurations. We believe that
future developments of both polarizable and explicit many-body models should continue in parallel
and would benefit from synergistic efforts aimed at integrating the best aspects of the two frameworks.
144. A many-body, fully polarizable approach to QM/MM simulations. E. Lambros, F. Lipparini, G.A. Cisneros,
F. Paesani. J. Chem. Theory Comput. 16, 7462 (2020).
We present a new development in quantum mechanics/molecular mechanics (QM/MM) methods by replacing
conventional MM models with data-driven many-body (MB) representations rigorously derived from high-level QM
calculations. The new QM/MM approach builds on top of mutually polarizable QM/MM schemes developed for
polarizable force fields with inducible dipoles and uses permutationally invariant polynomials to effectively account
for quantum-mechanical contributions (e.g., exchange-repulsion, and charge transfer and penetration) that are
difficult to describe by classical expressions adopted by conventional MM models. Using MB-pol and MB-DFT,
which include explicit 2B and 3B terms fitted to reproduce the corresponding CCSD(T) and PBE0 2B and 3B
energies for water, we demonstrate a smooth energetic transition as molecules are transferred between QM and
MM regions. By effectively elevating the accuracy of both the MM region and the QM/MM interface to that of the
QM region, the new QM/MB-MM approach achieves an accuracy comparable to that obtained with a fully QM
treatment of the entire system.
145. Data-driven many-body models with chemical accuracy for CH4/H2O mixtures. M. Riera, A. Hirales, R. Ghosh,
F. Paesani. J. Phys. Chem. B 124, 1127 (2020).
We present a new development in quantum mechanics/molecular mechanics (QM/MM) methods by replacing
conventional MM models with data-driven many-body (MB) representations rigorously derived from high-level
QM calculations. Many-body potential energy functions (PEFs) based on the TTM-nrg and MB-nrg
theoretical/computational frameworks are developed from coupled cluster reference data for neat methane
and mixed methane/water systems. It is shown that that the MB-nrg PEFs achieve subchemical accuracy in
the representation of individual many-body effects in small clusters and enables predictive simulations from
the gas to the liquid phase. Analysis of structural properties calculated from molecular dynamics simulations
of liquid methane and methane/water mixtures using both TTM-nrg and MB-nrg PEFs indicates that, while
accounting for polarization effects is important for a correct description of many-body interactions in the liquid
phase, an accurate representation of short-range interactions, as provided by the MB-nrg PEFs, is necessary
for a quantitative description of the local solvation structure in liquid mixtures.