52 research outputs found
Correcting density-driven errors in projection-based embedding
Projection-based embedding provides a simple and numerically robust framework for multiscale wavefunction-in-density-functional-theory (WF-in-DFT) calculations. The approach works well when the approximate DFT is sufficiently accurate to describe the energetics of the low-level subsystem and the coupling between subsystems. It is also necessary that the low-level DFT produces a qualitatively reasonable description of the total density, and in this work, we study model systems where delocalization error prevents this from being the case. We find substantial errors in embedding calculations on open-shell doublet systems in which self-interaction errors cause spurious delocalization of the singly occupied orbital. We propose a solution to this error by evaluating the DFT energy using a more accurate self-consistent density, such as that of Hartree-Fock (HF) theory. These so-called WF-in-(HF-DFT) calculations show excellent convergence towards full-system wavefunction calculations
Hybrid effects in field populations of the African monarch butterfly, Danaus chrysippus (L.) (Lepidoptera: Nymphalidae)
This is the final version. Available on open access from Oxford University Press via the DOI in this recordHeterosis, Haldane and Bateson-Dobzhansky-Muller effects have been widely documented
amongst a range of plants and animals. However, typically these effects are shown by taking
parents of known genotype into the laboratory and measuring components of the F1 progeny
under laboratory conditions. This leaves in doubt the real significance of such effects in the field.
Here we use the well-known colour pattern genotypes of the African Monarch or Queen (Danaus
chrysippus), which also control wing length, to test these effects both in the laboratory and in a
contact zone in the field. By measuring the wing lengths in animals of known colour pattern
genotype we show clear evidence for all three hybrid effects at the A and BC colour patterning
loci, and importantly, that these same effects persist in the same presumptive F1s when
measured in hybrid populations in the field. This demonstrates the power of a system in which
genotypes can be directly inferred in the field and highlights that all three hybrid effects can be
seen in the east African contact zone of this fascinating butterfly
Projector-Based Embedding Eliminates Density Functional Dependence for QM/MM Calculations of Reactions in Enzymes and Solution
Combined
quantum mechanics/molecular mechanics (QM/MM) methods
are increasingly widely utilized in studies of reactions in enzymes
and other large systems. Here, we apply a range of QM/MM methods to
investigate the Claisen rearrangement of chorismate to prephenate,
in solution, and in the enzyme chorismate mutase. Using projector-based
embedding in a QM/MM framework, we apply treatments up to the CCSDÂ(T)
level. We test a range of density functional QM/MM methods and QM
region sizes. The results show that the calculated reaction energetics
are significantly more sensitive to the choice of density functional
than they are to the size of the QM region in these systems. Projector-based
embedding of a wave function method in DFT reduced the 13 kcal/mol
spread in barrier heights calculated at the DFT/MM level to a spread
of just 0.3 kcal/mol, essentially eliminating dependence on the functional.
Projector-based embedding of correlated ab initio methods provides a practical method for achieving high accuracy
for energy profiles derived from DFT and DFT/MM calculations for reactions
in condensed phases
Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy
Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzymeâprodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells
Interactive molecular dynamics in virtual reality from quantum chemistry to drug binding: An open-source multi-person framework
© 2019 Author(s). As molecular scientists have made progress in their ability to engineer nanoscale molecular structure, we face new challenges in our ability to engineer molecular dynamics (MD) and flexibility. Dynamics at the molecular scale differs from the familiar mechanics of everyday objects because it involves a complicated, highly correlated, and three-dimensional many-body dynamical choreography which is often nonintuitive even for highly trained researchers. We recently described how interactive molecular dynamics in virtual reality (iMD-VR) can help to meet this challenge, enabling researchers to manipulate real-time MD simulations of flexible structures in 3D. In this article, we outline various efforts to extend immersive technologies to the molecular sciences, and we introduce "Narupa," a flexible, open-source, multiperson iMD-VR software framework which enables groups of researchers to simultaneously cohabit real-time simulation environments to interactively visualize and manipulate the dynamics of molecular structures with atomic-level precision. We outline several application domains where iMD-VR is facilitating research, communication, and creative approaches within the molecular sciences, including training machines to learn potential energy functions, biomolecular conformational sampling, protein-ligand binding, reaction discovery using "on-the-fly" quantum chemistry, and transport dynamics in materials. We touch on iMD-VR's various cognitive and perceptual affordances and outline how these provide research insight for molecular systems. By synergistically combining human spatial reasoning and design insight with computational automation, technologies such as iMD-VR have the potential to improve our ability to understand, engineer, and communicate microscopic dynamical behavior, offering the potential to usher in a new paradigm for engineering molecules and nano-architectures
Bedrock erosion by root fracture and tree throw: A coupled biogeomorphic model to explore the humped soil production function and the persistence of hillslope soils
In 1877, G. K. Gilbert reasoned that bedrock erosion is maximized under an intermediate soil thickness and declines as soils become thinner or thicker. Subsequent analyses of this âhumpedâ functional relationship proposed that thin soils are unstable and that perturbations in soil thickness would lead to runaway thinning or thickening of the soil. To explore this issue, we developed a numerical model that simulates the physical weathering of bedrock by root fracture and tree throw. The coupled biogeomorphic model combines data on conifer population dynamics, rootwad volumes, tree throw frequency, and soil creep from the Pacific Northwest (USA). Although not hardwired into the model, a humped relationship emerges between bedrock erosion and soil thickness. The magnitudes of the predicted bedrock erosion rates and their functional dependency on soil thickness are consistent with independent field measurements from a coniferous landscape in the region. Imposed perturbations of soil erosion during model runs demonstrate that where bedrock weathering is episodic and localized, hillslope soils do not exhibit runaway thinning or thickening. The pit-and-mound topography created by tree throw produces an uneven distribution of soil thicknesses across a hillslope; thus, although episodes of increased erosion can lead to temporary soil thinning and even the exposure of bedrock patches, local areas of thick soils remain. These soil patches provide habitat for trees and serve as nucleation points for renewed bedrock erosion and soil production. Model results also suggest that where tree throw is a dominant weathering process, the initial mantling of bedrock is not only a vertical process but also a lateral process: soil mounds created by tree throw flatten over time, spreading soil over bedrock surfaces
Conducting robust ecological analyses with climate data
Although the number of studies discerning the impact of climate change on ecological systems continues to increase, there has been relatively little sharing of the lessons learnt when accumulating this evidence. At a recent workshop entitled âUsing climate data in ecological researchâ held at the UK Met Office, ecologists and climate scientists came together to discuss the robust analysis of climate data in ecology. The discussions identified three common pitfalls encountered by ecologists: 1) selection of inappropriate spatial resolutions for analysis; 2) improper use of publically available data or code; and 3) insufficient representation of the uncertainties behind the adopted approach. Here, we discuss how these pitfalls can be avoided, before suggesting ways that both ecology and climate science can move forward. Our main recommendation is that ecologists and climate scientists collaborate more closely, on grant proposals and scientific publications, and informally through online media and workshops. More sharing of data and code (e.g. via online repositories), lessons and guidance would help to reconcile differing approaches to the robust handling of data. We call on ecologists to think critically about which aspects of the climate are relevant to their study system, and to acknowledge and actively explore uncertainty in all types of climate data. And we call on climate scientists to make simple estimates of uncertainty available to the wider research community. Through steps such as these, we will improve our ability to robustly attribute observed ecological changes to climate or other factors, while providing the sort of influential, comprehensive analyses that efforts to mitigate and adapt to climate change so urgently require
Evidence for differential effects of reduced and oxidised nitrogen deposition on vegetation independent of nitrogen load
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