Paesani Research Group

Laboratory for Theoretical and Computational Chemistry at UC San Diego  

202. MBX v1.2: Accelerating data-driven many-body molecular dynamics simulations. S. Gupta, E.F. Bull-Vulpe,

        H. Agnew, S. Iyer, X. Zhu, R. Zhou, C. Knight, F. Paesani, J. Chem. Theory Comput. In press. [link]

The MBX software provides an advanced platform for molecular dynamics simulations, leveraging state-of-the-art MB-pol

and MB-nrg data-driven many-body potential energy functions. Developed over the past decade, these potential energy

functions integrate physics-based and machine-learned many-body terms trained on electronic structure data calculated

at the ``gold standard'' coupled cluster level of theory. Recent advancements in MBX have focused on optimizing its

performance, resulting in the release of MBX v1.2. While the inherently many-body nature of MB-pol and MB-nrg ensures

high accuracy, it poses computational challenges. MBX v1.2 addresses these challenges with significant performance

improvements, including enhanced parallelism that fully harnesses the power of modern multicore CPUs. These

advancements enable simulations on nanosecond timescales for condensed-phase systems, significantly expanding the

scope of high-accuracy, predictive simulations of complex molecular systems powered by data-driven many-body potential

energy functions.

198. Dissecting the molecular structure of the air/ice interface from quantum simulations of the sum-frequency

        generation spectrum. R. Rashmi, F. Paesani, J. Am. Chem. Soc. 147, 1903 (2025). [link]

At the ice surface, water molecules form a quasi-liquid layer (QLL) with distinct properties from the bulk. Despite numerous

experimental and theoretical studies, the molecular-level understanding of this layer has remained elusive.In this work, we use

state-of-the-art quantum dynamics simulations with a realistic data-driven many- body potential to dissect the vibrational

sum-frequency generation (vSFG) spectrum in terms of contributions arising from individual molecular layers, orientations, and

hydrogen-bonding topologies that determine the QLL properties. The agreement between experimental and simulated spectra

provides a realistic view of the evolution of the QLL as a function of temperature without the need for empirical adjustments.

At lower temperatures, the emergence of specific features in the vSFG spectrum points to surface restructuring, resulting in

mixed ice Ih and ice Ic nanodomains at the surface, which may vary depending on how the air/ice interface is prepared. This

work not only underscores the critical role of many-body interactions and nuclear quantum effects in understanding ice surfaces

but also provides a definitive molecular-level picture of the QLL, which plays a central role in multiphase and heterogeneous

processes of relevance to a range of fields, including atmospheric chemistry, cryopreservation, and materials science.

204. Nuclear quantum effects and the Grotthuss mechanism dictate the pH of liquid water.

        S. Dasgupta, G. Cassone, F. Paesani, under review. [link]

Water’s ability to autoionize into hydronium (H3O+) and hydroxide (OH) ions dictates the acidity or basicity of aqueous

solutions, influencing the reaction pathways of many chemical and biochemical processes. In this study, we determine the

molecular mechanism of the autoionization process by leveraging both the computational efficiency of a deep neural

network potential trained on highly accurate data calculated within density-corrected density functional theory and the

ability of enhanced sampling techniques to ensure a comprehensive exploration of the underlying multidimensional

free-energy landscape. By properly accounting for nuclear quantum effects, our simulations provide an accurate estimate

of autoionization constant of liquid water (pKw = 13.71 ± 0.16), offering a real- istic molecular-level picture of the

autoionization process and emphasizing its quantum-mechanical nature. Importantly, our simulations highlight the central

role played by the Grotthuss mechanism in stabilizing solvent-separated ion pair configurations, revealing its profound

impact on acid-base equilibria in aqueous environments.

© Paesani Research Group. All rights reserved.

Publications 2025

200. Constraints on the location of the liquid–liquid critical point in water. F. Sciortino, Y. Zhai, S.L. Bore, F. Paesani,

        Nat. Phys. in press. [link]

Over the past three decades, advancements in computational modeling – particularly through the advent of data-driven

many-body potentials rigorously derived from “first principles” and augmented by the efficiency of neural networks – have

significantly enhanced the accuracy of molecular simulations, enabling the exploration of the phase behavior of water with

unprecedented realism. Our study leverages these computational advances to probe the elusive liquid-liquid transition in

supercooled water. For the first time, microsecond-long simulations with chemical accuracy, conducted over several years,

provide compelling evidence that water indeed exists in two discernibly distinct liquid states at low temperature and high

pressure. By pinpointing a realistic estimate for the location of the liquid-liquid critical point at ~200 K and ~1050 atm, our

study not only advances current understanding of water’s anomalous behavior but also establishes a basis for experimental

validation. Importantly, our simulations indicate that the liquid-liquid critical point falls within tem- perature and pressure

ranges that could potentially be experimentally probed in water nanodroplets, opening the possibility for direct measurements.

203. Structure-activity relationships in ether-functionalized solid-state metal-organic framework electrolytes.

        A.U. Mu, V.V. Singh, H. Kim, D.J. Lee, N. Kim, C.X. Ruff, A. Levy, T.A. Young, F. Paesani, S.M. Cohen, T.A. Pascal,

        Z. Chen, under review. [link]

The structure-property relationships of metal-organic framework (MOF) based solid-state electrolytes are not well understood.

Herein, a systematic investigation of twelve Zr(IV)-based UiO-66 MOFs with varying ether-chain functional groups was carried out to elucidate the critical microscopic interactions that facilitate improved solid-state electrolyte performance. Enhanced sampling molecular dynamics

(MD) simulations were employed and revealed a three-tier ion hopping mechanism: linker-linker hopping, linker-counterion

hopping, and counterion-counterion hopping. As a result, we were able to tune the ion conductivities by means of rationally

manipulating the counterion distributions, linker binding strengths, and the configurational entropy (multi-variability of the

linkers). The resulting performance of these MOF-based solid-state electrolytes was significantly enhanced, with a methoxy-

functionalized framework (UiO-66-L1-100) achieving high ionic conductivities of 2.32×10-4 S/cm and 2.07×10-3 S/cm at 30 °C

and 90 °C, respectively, a magnitude greater than other all-solid-state MOF electrolyte systems. The electrolyte stability was

evaluated with LiIn|LPSCl|MOF:LiTFSI|LPSCl|LiIn symmetric cells, showing excellent Li plating/stripping processes.

199. Electroreduction-driven formation and connectivity of polyoxometalate coordination networks.

        H. Chang, L. Chen, E. Samolova, Y. Pan, K.A. Acosta, C.E.Lemmon, M. Gembicky, F. Paesani, A.M. Schimpf,

        Inorg. Chem. 64, 1630 (2025). [link]

We present the synthesis of metal oxide coordination networks based on Preyssler-type polyoxoanions ([NaP5W30O110]14− and

[NaP5MoW29O110]14−) bridged with metal–aquo complexes ([M(H2O)n]m+, Mm+ = Co2+, Ni2+, Zn2+, Y3+), induced by

electrochemical reduction. Networks bridged with first-row transition metals are isostructural with a previously reported Co-bridged

structure, while the Y3+–bridged structure is new. All networks feature an uncommon binding motif of the metal cation to the

oxygen atoms at cap positions, which we hypothesize is due to increased electron density at the cap upon reduction. Oxidation of

a Zn2+–bridged network results in a new structure in which Zn2+–Ocap bonds are lost, indicating the importance of reduction in

the connectivity of these polyoxometalate coordination networks..

201. Revealing water structure at neutral and charged graphene/water interfaces through quantum simulations of

        sum-frequency generation spectra. R. Rashmi, T.O. Balogun, G. Azom, H. Agnew, R. Kumar, F. Paesani,

        ACS Nano. 19, 4876 (2025). [link]

Leveraging the realism of the MB-pol data-driven many-body potential and advanced path-integral quantum dynamics, we

analyze the vibrational sum-frequency generation (vSFG) spectrum of graphene/water interfaces under varying surface

charges. Our quantum simulations reveal a distinctive dangling OH peak in the vSFG spectrum at neutral graphene,

consistent with recent experimental findings yet markedly different from earlier studies. As the graphene surface becomes

positively charged, interfacial water molecules reorient, decreasing the intensity of the dangling OH peak as the OH groups

turn away from the graphene.In contrast, water molecules orient their OH bonds toward negatively charged graphene, leading

to a prominent dangling OH peak in the corresponding vSFG spectrum. This charge-induced reorganization generates a

diverse range of hydrogen-bonding topologies at the interface, driven by variations in the underlying electrostatic interactions.

Remarkably, these structural changes extend into deeper water layers, creating an unequal distribution of molecules with OH

bonds pointing toward and away from the graphene sheet.

205. Density-functionalized QM/MM delivers chemical accuracy for solvated systems. X. Chen, J. Martinez, X. Shao,

         M. Riera, F. Paesani, O. Andreussi, M. Pavanello, under review. [link]

We present a reformulation of QM/MM as a fully quantum mechanical theory of interacting subsystems, all treated at

the level of density functional theory (DFT). For the MM subsystem, which lacks orbitals, we assign an ad hoc electron

density and apply orbital-free DFT functionals to describe its quantum properties. The interaction between the QM and

MM subsystems is also treated using orbital-free density functionals, accounting for Coulomb interactions, exchange,

correlation, and Pauli repulsion. Consistency across QM and MM subsystems is ensured by employing data-driven,

many-body MM force fields that faithfully represent DFT functionals. Applications to water-solvated systems demonstrate

that this approach achieves unprecedented, very rapid convergence to chemical accuracy as the size of the QM

subsystem increases. We validate the method with several pilot studies, including water bulk, water clusters

(prism hexamer and pentamers), solvated glucose, a palladium aqua ion, and a wet monolayer of MoS2.