The Paesani Research Group

Laboratory for Theoretical and Computational Chemistry at UC San Diego  

117. Preordering of water is not needed for ice recognition by hyperactive antifreeze proteins. A. Hudait,

        D.R. Moberg, Y. Qiu, N. Odendahl, F. Paesani, V. Molinero, Proc. Natl. Acad. Sci. U.S.A. 115, 8266 (2018). [link]

Antifreeze proteins (AFPs) inhibit ice growth in organisms living in cold environments. It has been hypothesized

that the binding of hyperactive AFPs to ice is facilitated by preordering of water at the ice-binding site (IBS) of

the protein in solution. Here we use multi-resolution simulations to unravel the mechanism by which TmAFP

recognizes and binds ice. We find ice recognition occurs by slow diffusion of the protein to achieve the proper

orientation with respect to the ice surface, followed by fast collective organization of the hydration water at the

IBS to form an anchored clathrate motif that latches the protein to the ice surface. We compute, for the first time,

the infrared and Raman spectra of water in the anchored clathrate motif. The signatures of the OH-stretch of

water in the anchored clathrate motif can be distinguished from those of bulk liquid in the Raman spectra, but

not in the infrared spectra. We thus suggest that Raman spectroscopy may be used to probe the anchored

clathrate order at the ice-binding surface of INP aggregates.

115. Isomeric equilibria, nuclear quantum effects, and vibrational spectra of M+(H2O)n=1-3 clusters, with M = Li, Na,

        K, Rb, and Cs, through many-body representations. M. Riera, S.E. Brown, F. Paesani, J. Phys. Chem. A 122,

        5811 (2018). [link]

This study presents a systematic analysis of isomeric equilibria for small M+(H2O)n clusters, with

M = Li, Na, K, Rb, and Cs, from 0 K to 200 K. To determine the relative stability of different isomers

of each M+(H2O)n cluster as a function of temperature, replica exchange simulations are carried out

at both classical and quantum levels with our recently developed many-body MB-nrg potential

energy functions. Anharmonic vibrational spectra are then calculated within the local monomer

approximation and found to be in agreement with the available experimental data. The present

analysis indicates that nuclear quantum effects become increasingly important for larger M+(H2O)n

clusters due to competing ion-water and water-water interactions along with the interplay between

energetic and entropic effects. Our study represents a further step toward the development of a

consistent picture of ion hydration from the gas to the condensed phase.

112. Ice-nucleating and antifreeze proteins recognize ice through a diversity of anchored clathrate and ice-like

        motifs. A. Hudait, N. Odendahl, Y. Qiu, F. Paesani, V. Molinero. J. Am. Chem. Soc. 140, 4905 (2018). [link]

Cold-adapted organisms produce antifreeze and ice-nucleating proteins to prevent and promote

ice formation. Here, we use molecular simulations to elucidate the ice-binding motifs of hyperactive

insect AFPs and a model INP of Ps. syringae. We find that insect AFPs recognize ice through anchored

clathrate motifs distinct from that of MpAFP. By performing simulations of ice nucleation by PsINP,

we identify two distinct ice-binding sites on opposite sides of the β-helix. The ice nucleating sequences

identified in the simulations agree with those previously proposed for the closely related INP of Ps.

borealis based on the structure of the protein. The simulations indicate that these sites have

comparable ice nucleating efficiency, but distinct binding motifs, controlled by the amino acid sequence:

one is an-chored clathrate and the other ice-like. We conclude that anchored clathrate and ice-like

motifs can be equally effec-tive for binding proteins to ice and promoting ice nucleation.

© Paesani Research Group. All rights reserved.

Publications 2018

103. Vibrational spectra of halide-water dimers: Insights on ion hydration from full-dimensional quantum

        calculations on many-body potential energy surfaces. P. Bajaj, X.-G. Wang, T. Carrington, Jr., F. Paesani,

        J. Chem. Phys. 148, 102321 (2018). [link]

Full-dimensional vibrational spectra are calculated for both X-(H2O) and X-(D2O) dimers (X = F, Cl, Br, I) at the

quantum-mechanical level. The calculations are carried out on two sets of recently developed potential

energy functions (PEFs), namely, Thole-type model energy (TTM-nrg) and many-body energy (MB-nrg),

using the symmetry-adapted Lanczos algorithm with a product basis set including all six vibrational

coordinates. For all dimers, the MB-nrg vibrational spectra are in close agreement with the available

experimental data, correctly reproducing anharmonic and nuclear quantum effects. The comparison

between the TTM-nrg and MB-nrg results reinforces the notion that an accurate representation of both

short-range interactions associated with electron density overlap and long-range many-body electrostatic

interactions is necessary for a correct description of hydration phenomena at the molecular level.

104. Transmission electron microscopy reveals deposition of metal oxide coatings onto metal-organic

        frameworks. M.S. Denny, Jr., L.R. Parent, J.P. Patterson, S.K. Meena, C.H. Pham, P. Abellan, Q.M. Ramasse,  

        F. Paesani, N.C. Gianneschi, S.M. Cohen, J. Am. Chem. Soc. 140, 1348 (2018). [link]

In this collaboration with the Gianneschi and Cohen groups, we combine several analytical methods, most notably

inductively coupled plasma mass spectrometry (ICP-MS) and transmission electron microscopy (TEM) with

computer simulations to reveal that metal ion deposition on the surface of UiO-66 MOFs occurs in the form of

nanoscale metal oxides, rather than yielding exchanged metal sites within the MOFs, as was previously reported.

By contrast, these combined methods do confirm that ligand-based PSE can occur in these MOFs. These findings

provide new insight into the postsynthetic manipulation of MOF materials, highlight the importance of rigorously

characterizing these materials to correctly assign their composition and structure, and provide a new route to

making hybrid solids with a MOF@metal oxide architecture.

105. Electron affinity of liquid water. A.P. Gaiduk, T.A. Pham, M. Govoni, F. Paesani, G. Galli, Nat. Commun. 9, 247

        (2018). [link]

Understanding redox and photochemical reactions in aqueous environments requires a precise knowledge

of the ionization potential and electron affinity of liquid water. The former has been measured, but not the

latter. We predict the electron affinity (EA) of liquid water and of its surface from first principles, coupling

path-integral molecular dynamics with ab initio potentials, and many-body perturbation theory. Our results

for the surface agree well with recent pump-probe spectroscopy measurements on amorphous ice. Those

for the bulk differ from several estimates adopted in the literature, which we critically revisit. We show that

the ionization potential of the bulk and surface are almost identical; instead their EAs differ substantially,

with the conduction band edge of the surface much deeper in energy than that of the bulk. We also discuss

the significant impact of nuclear quantum effects and vibronic coupling on the fundamental gap and band

edges of the liquid.

106. Second-order vibrational lineshapes from the air/water interface. P. Ohno, H.-F. Wang, F. Paesani, J.L. Skinner,

        F.M. Geiger, J. Phys. Chem. A 122, 4457 (2018). [link]

We explore by means of mathematical modeling how absorptive-dispersive mixing between

the second- and third-order terms modify the imaginary χ(2)total responses from air/water interfaces

under conditions of varying minute charge densities and ionic strength. To do so, we use

published Im(χ(2)) and χ(3) spectra of the neat air/water interface that were obtained either from

computations or experiments. We find that the χ(2)total spectral lineshapes are considerably

sensitive to χ(2) and χ(3) mixing at interfacial charge densities as low as 0.01% of a monolayer of

water molecules, especially in the 3100 cm-1 to 3300 cm-1 frequency region. The role of

short-range static dipole potentials was examined under conditions mimicking brine. Our results

indicate that surface potentials, if indeed present at the air/water interface, manifest themselves

spectroscopically in the tightly bonded H-bond network observable in the 3200 cm-1 frequency


107. Engineering the entropy-driven free-energy landscape of a dynamic, nanoporous protein assembly.

        R. Alberstein, Y. Suzuki, F. Paesani, F.A. Tezcan, Nature Chem. 10, 732 (2018). [link]

The sophistication of all living systems hinges at the molecular level on the ability of proteins and

protein assemblies to alter their structures in response to physical and chemical stimuli. Although

there have been notable advances in the design of protein structures, the de novo design of

stimuli-responsive dynamic protein assemblies that predictably switch between discrete conformations

remains an essential but difficult goal. Here, we describe the first example of a synthetic 2D lattice

self-assembled from C98RhuA proteins, whose free energy landscape associated with the structural

dynamics is fully determined by computer simulations, which allows us to predictably engineer its

conformational switching behavior. From all-atom molecular dynamics simulations is established that

the free-energy landscape is predominantly governed by solvent reorganization entropy. Subsequent

redesign of the protein surface with conditionally repulsive electrostatic interactions enable us to

predictably perturb the free-energy landscape.

108. Assessing many-body effects of water self-ion. 1. OH-(H2O)n clusters. C.K. Egan, F. Paesani, J. Chem. Theory

        Comput. 14, 1982 (2018). [link]

In this study, we investigate the importance of many-body effects in the hydration of the hydroxide ion (OH)

through a systematic analysis of the many-body expansion of the interaction energy carried out at the

CCSD(T) level of theory, in the complete basis set limit, for the low-lying isomers of OH(H2O)n clusters,

with n = 1 − 5. This is accomplished by partitioning individual fragments extracted from the whole clusters

into “groups” that are classified by both the number of OH and H2O molecules and the hydrogen bonding

connectivity within each fragment. Our analysis emphasizes the importance of a many-body representation

of inductive electrostatics and charge transfer in modeling OH hydration. A comparison between CCSD(T)

and various DFT models demonstrates that range-separated, dispersion corrected, hybrid functionals exhibit

the highest accuracy, while GGA functionals, with or without dispersion corrections, are inadequate to describe

the interactions between OHand water.

109. Bulk contributions modulate the sum-frequency generation spectra of water on model sea-spray aerosols.

        S.K. Reddy, R. Thiraux, B.A. Wellen Rudd, L. Lin, T. Adel, T. Joutsuka, F.M. Geiger, H.C. Allen, A. Morita, F. Paesani,

        CHEM. 4, 1629 (2018). [link]

Vibrational sum-frequency generation (vSFG) spectroscopy is used to determine the molecular

structure of water at the interface of palmitic acid monolayers. Both measured and calculated

spectra display specific features due to third-order contributions to the vSFG response which are

associated with finite interfacial electric potentials. We demonstrate that theoretical modeling enables

to separate the third-order contributions, thus allowing for a systematic analysis of the strictly

surface-sensitive, second-order component of the vSFG response. This study provides fundamental,

molecular-level insights into the interfacial structure of water in a neutral surfactant system with

relevance to single layer bio-membranes and environmentally relevant sea-spray aerosols.

Furthermore, our analysis emphasizes the key role that computer simulations can play in interpreting

vSFG spectra and revealing microscopic details of water at complex interfaces.

110. Comparison of permutationally invariant polynomials, neural networks, and Gaussian approximation

        potentials in representing water interactions through many-body expansions. T.T. Nguyen, E. Székely,

        G. Imbalzano, J. Behler, G. Csányi, M. Ceriotti, A.W. Götz, F. Paesani, J. Chem. Phys. 148, 241725 (2018). [link]

Building on the accuracy of the MB-pol many-body potential energy function, we investigate here the

performance of permutationally invariant polynomials, neural networks, and Gaussian approximation

potentials in representing water two-body and three-body interaction energies. Our analysis shows that all

three analytical representations exhibit similar levels of accuracy in reproducing both two-body and

three-body reference data as well as interaction energies of small water clusters obtained from calculations

carried out at the coupled cluster level of theory. These results demonstrate the synergy between interatomic

potentials formulated in terms of a many-body expansion, such as MB-pol, that are physically sound and

transferable, and machine-learning techniques that provide a flexible framework to approximate the

short-range interaction energy terms.

111. Temperature-dependence of the air/water interface revealed by polarization-sensitive sum-frequency

        generation spectroscopy. D.R. Moberg, S.C. Straight, F. Paesani, J. Phys. Chem. B 122, 4356 (2018). [link]

The temperature dependence of the vibrational sum-frequency generation (vSFG) spectra of the

air/water interface is investigated using many-body molecular dynamics (MB-MD) simulations

performed with the MB-pol potential energy function. The total vSFG spectra calculated for different

polarization combinations are then analyzed in terms of molecular auto-correlation and cross-correlation

contributions. To provide molecular-level insights into interfacial hydrogen-bonding topologies, which

give rise to specific spectroscopic features, the vSFG spectra are further investigated by separating

contributions associated with water molecules donating 0, 1, or 2 hydrogen bonds to neighboring

water molecules. This analysis suggests that the low frequency shoulder of the free OH peak which

appears at ~3600 cm−1 is primarily due to intermolecular couplings between both singly and doubly

hydrogen-bonded molecules.

113. Guest-dependent stabilization of the low-spin state in spin-crossover metal-organic frameworks.

        C.H. Pham, F. Paesani, Inorg. Chem. 57, 9839 (2018). [link]

Computer simulations are carried out to characterize the variation of spin crossover (SCO) behavior of the

prototypical {Fe(pz)[Pt(CN)4]} metal-organic framework (MOF) upon adsorption of chemically and structurally

different guest molecules. A detailed analysis of both strength and anisotropy of guest molecule-framework

interactions reveals direct correlations between the mobility of the guest molecules inside the MOF pores,

the rotational mobility of the pyrazine rings of the framework, and the stabilization of the low-spin state of the

material. Based on these correlations, precise molecular criteria are established for predicting the spin state

of {Fe(pz)[Pt(CN)4]} upon guest adsorption. Finally, predictions of the SCO temperature upon adsorption

of various toxic gases demonstrate that in silico modeling can provide fundamental insights and design

principles for the development of spin-crossover MOFs for applications in gas detection and chemical sensing.

114. Solvation-guided design of fluorescent probes for discrimination of amyloids. K.J. Cao, K.M. Elbel, J.L. Cifelli,

        J. Cirera, C.J. Sigurdson, F. Paesani, E.A. Theodorakis, J. Yang, Sci. Rep. 8, 6950 (2018). [link]

In this study, we present a series of amino-aryl cyanoacrylate (AACA) fluorophores that show a turn-on

fluorescence signal upon binding to amyloids in solution and in tissue. Using a theoretical model for

environmental sensitivity of fluorescence together with ab initio computational modeling of the effects

of polar environment on electron density distribution and conformational dynamics, we designed,

synthesized, and evaluated a set of fluorophores that (1) bind to aggregated forms of Alzheimer’s-related

β-amyloid peptides with low micromolar to high nanomolar affinities and (2) have the capability to

fluorescently discriminate different amyloids based on differences in amino acid composition within the

binding pocket through exploitation of their solvatochromic properties. These studies showcase the rational

design of a family of amyloid-binding imaging agents that could be integrated with new optical approaches for

the clinical diagnosis of amyloidoses, which could aid in the selection of a proper course for treatment.

116. Electron-hole theory of the effect of quantum nuclei on the X-ray absorption spectrum of liquid water.

        Z. Sun, L. Zheng, M. Chen, M.L. Klein, F. Paesani, X. Wu, Phys. Rev. Lett. 121, 137401 (2018). [link]

Based on electron-hole excitation theory, we investigate the X-ray absorption spectral signature of nuclear

quantum effect in liquid water, whose molecular structure is simulated by path-integral molecular dynamics

using the MB-pol model. Compared to spectra generated from classically modeled water structure, quantum

nuclei has important effect on spectra in terms of both the spectral energies and their line shapes. At the

short-range ordering of H-bond network, the delocalized protons increase the fluctuations on the intramolecular

covalency and broaden the pre-edge of the spectra. For intermediate-range and long-range orderings, the

observed red and blue shifts of the main-edge and post-edge are attributed to the so-called competing

quantum effects, under which both the weak and well-formed H-bonds are promoted. The theoretical spectra

are in nearly quanitative agreement with the available experimental data.


118. Molecular-level interpretation of vibrational spectra of ice ordered phases. D.R. Moberg, P.J. Sharp, F. Paesani,

        J. Phys. Chem. B 122, 10572 (2018). [link]

We build on results from our previous investigation into ice Ih using a combination of classical many-body

molecular dynamics (MB-MD) and normal mode (NM) calculations to obtain molecular level information on

the spectroscopic signatures in the OH stretching region for all seven of the known ordered crystalline ice

phases. The classical MB-MD spectra are shown to capture the important spectral features by comparing

with experimental Raman spectra. From the normal mode calculations, measures of the amount of symmetric

and antisymmetric stretching are calculated for each ice, as well as an approximation of how localized each

mode is. As in ice Ih, it is found that most of the other ordered ice phases have highly delocalized modes and

their spectral features cannot, in general, be described in terms of molecular normal modes. The lone exception

is ice VIII, the densest crystalline ice phase, for which the symmetry index shows a clear separation of

symmetric and antisymmetric stretching modes giving rise to two distinct features.

119. Disentangling coupling effects in the infrared spectra of liquid water. K.M. Hunter, F.A. Shakib, F. Paesani,

        J. Phys. Chem. B 122, 10754 (2018). [link]

A quantitative characterization of intermolecular and intramolecular couplings that modulate the OH-stretch

vibrational band in liquid water has so far remained elusive. Here, we take up this challenge by combining the

centroid molecular dynamics formalism, which accounts for nuclear quantum effects, with the MB-pol potential

energy function, which accurately reproduces the properties of water across all phases, to model the IR spectra

of various isotopic water solutions with different levels of vibrational couplings, including those that cannot be

probed experimentally. Analysis of the different IR OH-stretch lineshapes provides direct evidence for the partially

quantum-mechanical nature of hydrogen bonds in liquid water. Furthermore, we quantitatively demonstrate that

intramolecular coupling, which results in Fermi resonances due to the mixing between HOH-bend overtones and

OH-stretch fundamentals, are responsible for the shoulder located at ~3250 cm-1 of the IR OH-stretch band of

liquid water.

120. The neat water-vapour interface: Proton continuum and the non-resonant background. S. Sengupta,

        D.R. Moberg, F. Paesani, E. Tyrode, J. Phys. Chem. Lett. 9, 6744 (2018). [link]

Whether the surface of neat water is “acidic” or “basic” remains an active and controversial field of research.

Most of the experimental evidence supporting the preferential adsorption of H3O+ ions stems from non-linear

optical spectroscopy methods typically carried out at extreme pH conditions (pH < 1). Here, we use vibrational

sum frequency spectroscopy (VSFS) to target the “proton continuum”, an unexplored frequency range

characteristic of hydrated protons and hydroxide ions. The VSFS spectra of neat water show a broad and

non-zero signal intensity between 1700 cm-1 and 3000 cm-1 in the three different polarization combinations

examined. By comparing the SF response of water with that from dilute HCl and NaOH aqueous solutions,

we conclude the intensity does not originate from either adsorbed H3O+ or OH- ions. Contributions from the

non-resonant background are then critically considered by comparing the experimental results with many-body

molecular dynamics (MB-MD) simulated spectra.

121. The orientational distribution of free O-H groups of interfacial water is exponential. S. Sun, F. Tang, S. Imoto,

        D.R. Moberg, T. Ohto, F. Paesani, M. Bonn, E. Backus, Y. Nagata, Phys. Rev. Lett. 121, 246101 (2018). [link]

In this collaborative study, the orientational distribution of free O-H (O-D) groups at the water-air

interface is investigated using combined molecular dynamics (MD) simulations and sum-frequency

generation (SFG) experiments. The average angle of the free O-H groups, relative to the surface

normal, is found to be substantially larger than previous estimates of 30-40o. This discrepancy can

be traced to erroneously assumed Gaussian/stepwise orientational distributions of free O-H groups.

Instead, MD simulation and SFG measurement reveal a broad and exponentially decaying orientational

distribution. The broad orientational distribution indicates the presence of the free O-H group pointing

down to the bulk. We ascribe the origin of such free O-H groups to the presence of capillary waves

on the water surface.