34 research outputs found
Analytic Gradients for Complete Active Space Pair-Density Functional Theory
Analytic gradient routines are a desirable feature for quantum mechanical
methods, allowing for efficient determination of equilibrium and transition
state structures and several other molecular properties. In this work, we
present analytical gradients for multiconfiguration pair-density functional
theory (MC-PDFT) when used with a state-specific complete active space
self-consistent field reference wave function. Our approach constructs a
Lagrangian that is variational in all wave function parameters. We find that
MC-PDFT locates equilibrium geometries for several small- to medium-sized
organic molecules that are similar to those located by complete active space
second-order perturbation theory but that are obtained with decreased
computational cost
Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.
PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils
The OpenMolcas Web: A Community-Driven Approach to Advancing Computational Chemistry
The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations
Relativistic Kramers-Unrestricted Exact-Two-Component Density Matrix Renormalization Group
Mechanisms involved in the triggering of neutrophil extracellular traps (NETs) by Candida glabrata during planktonic and biofilm growth
Abstract Candida spp. adhere to medical devices, such as catheters, forming drug-tolerant biofilms that resist killing by the immune system. Little is known about how C. glabrata, an emerging pathogen, resists attack by phagocytes. Here we show that upon encounter with planktonic (non-biofilm) C. glabrata, human neutrophils initially phagocytose the yeast and subsequently release neutrophil extracellular traps (NETs), complexes of DNA, histones, and proteins capable of inhibiting fungal growth and dissemination. When exposed to C. glabrata biofilms, neutrophils also release NETs, but significantly fewer than in response to planktonic cells. Impaired killing of biofilm parallels the decrease in NET production. Compared to biofilm, neutrophils generate higher levels of reactive oxygen species (ROS) when presented with planktonic organisms, and pharmacologic inhibition of NADPH-oxidase partially impairs NET production. In contrast, inhibition of phagocytosis nearly completely blocks NET release to both biofilm and planktonic organisms. Imaging of the host response to C. glabrata in a rat vascular model of infection supports a role for NET release in vivo. Taken together, these findings show that C. glabrata triggers NET release. The diminished NET response to C. glabrata biofilms likely contributes to the resilience of these structured communities to host defenses
Multiconfiguration Pair-Density Functional Theory Spectral Calculations Are Stable to Adding Diffuse Basis Functions
Time-dependent
Kohn–Sham density functional theory (TD-KS-DFT)
is useful for calculating electronic excitation spectra of large systems,
but the low-energy spectra are often complicated by artificially lowered
higher-energy states. This affects even the lowest energy excited
states. Here, by calculating the lowest energy spin-conserving excited
state for atoms from H to K and for formaldehyde, we show that this
problem does not occur in multiconfiguration pair-density functional
theory (MC-PDFT). We use the tPBE on-top density functional, which
is a translation of the PBE exchange-correlation functional. We compare
to a robust multireference method, namely, complete active space second-order
perturbation theory (CASPT2), and to TD-KS-DFT with two popular exchange-correlation
functionals, PBE and PBE0. We find for atoms that the mean unsigned
error (MUE) of MC-PDFT with the tPBE functional improves from 0.42
to 0.40 eV with a double set of diffuse functions, whereas the MUEs
for PBE and PBE0 drastically increase from 0.74 to 2.49 eV and from
0.45 to 1.47 eV, respectively
Correction to “Multiconfiguration Pair-Density Functional Theory Spectral Calculations Are Stable to Adding Diffuse Basis Functions”
Correction to “Multiconfiguration Pair-Density Functional
Theory Spectral Calculations Are Stable to Adding Diffuse Basis Functions
Multiconfiguration Pair-Density Functional Theory Is as Accurate as CASPT2 for Electronic Excitation
A correct description of electronically
excited states is critical
to the interpretation of visible–ultraviolet spectra, photochemical
reactions, and excited-state charge-transfer processes in chemical
systems. We have recently proposed a theory called multiconfiguration
pair-density functional theory (MC-PDFT), which is based on a combination
of multiconfiguration wave function theory and a new kind of density
functional called an on-top density functional. Here, we show that
MC-PDFT with a first-generation on-top density functional performs
as well as CASPT2 for an organic chemistry database including valence,
Rydberg, and charge-transfer excitations. The results are very encouraging
for practical applications
Nonintuitive Diabatic Potential Energy Surfaces for Thioanisole
Diabatization of potential energy
surfaces is a technique that
enables convenient molecular dynamics simulations of electronically
nonadiabatic processes, but diabatization itself is nonunique and
can be inconvenient; the best methods to achieve diabatization are
still under study. Here, we present the diabatization of two electronic
states of thioanisole in the S–CH<sub>3</sub> bond stretching
and C–C–S–C torsion two-dimensional nuclear coordinate
space containing a conical intersection. We use two systematic methods:
the (orbital-dependent) 4-fold way and the (orbital-free) Boys localization
diabatization method. These very different methods yield strikingly
similar diabatic potential energy surfaces that cross at geometries
where the adiabatic surfaces are well separated and do not exhibit
avoided crossings, and the contours of the diabatic gap and diabatic
coupling are similar for the two methods. The validity of the diabatization
is supported by comparing the nonadiabatic couplings calculated from
the diabatic matrix elements to those calculated by direct differentiation
of the adiabatic states