DiffHopp: A Graph Diffusion Model for Novel Drug Design via Scaffold Hopping

Scaffold hopping is a drug discovery strategy to generate new chemical entities by modifying the core structure, the \emph{scaffold}, of a known active compound. This approach preserves the essential molecular features of the original scaffold while introducing novel chemical elements or structural features to enhance potency, selectivity, or bioavailability. However, there is currently a lack of generative models specifically tailored for this task, especially in the pocket-conditioned context. In this work, we present DiffHopp, a conditional E(3)-equivariant graph diffusion model tailored for scaffold hopping given a known protein-ligand complex

On the Expressive Power of Geometric Graph Neural Networks

The expressive power of Graph Neural Networks (GNNs) has been studied extensively through the Weisfeiler-Leman (WL) graph isomorphism test. However, standard GNNs and the WL framework are inapplicable for geometric graphs embedded in Euclidean space, such as biomolecules, materials, and other physical systems. In this work, we propose a geometric version of the WL test (GWL) for discriminating geometric graphs while respecting the underlying physical symmetries: permutations, rotation, reflection, and translation. We use GWL to characterise the expressive power of geometric GNNs that are invariant or equivariant to physical symmetries in terms of distinguishing geometric graphs. GWL unpacks how key design choices influence geometric GNN expressivity: (1) Invariant layers have limited expressivity as they cannot distinguish one-hop identical geometric graphs; (2) Equivariant layers distinguish a larger class of graphs by propagating geometric information beyond local neighbourhoods; (3) Higher order tensors and scalarisation enable maximally powerful geometric GNNs; and (4) GWL's discrimination-based perspective is equivalent to universal approximation. Synthetic experiments supplementing our results are available at https://github.com/chaitjo/geometric-gnn-dojoComment: NeurIPS 2022 Workshop on Symmetry and Geometry in Neural Representation

Benchmarking Generated Poses: How Rational is Structure-based Drug Design with Generative Models?

Deep generative models for structure-based drug design (SBDD), where molecule generation is conditioned on a 3D protein pocket, have received considerable interest in recent years. These methods offer the promise of higher-quality molecule generation by explicitly modelling the 3D interaction between a potential drug and a protein receptor. However, previous work has primarily focused on the quality of the generated molecules themselves, with limited evaluation of the 3D molecule \emph{poses} that these methods produce, with most work simply discarding the generated pose and only reporting a "corrected" pose after redocking with traditional methods. Little is known about whether generated molecules satisfy known physical constraints for binding and the extent to which redocking alters the generated interactions. We introduce PoseCheck, an extensive analysis of multiple state-of-the-art methods and find that generated molecules have significantly more physical violations and fewer key interactions compared to baselines, calling into question the implicit assumption that providing rich 3D structure information improves molecule complementarity. We make recommendations for future research tackling identified failure modes and hope our benchmark can serve as a springboard for future SBDD generative modelling work to have a real-world impact

Scheme for the implementation of a universal quantum cloning machine via cavity-assisted atomic collisions in cavity QED

We propose a scheme to implement the $1\to2$ universal quantum cloning machine of Buzek et.al [Phys. Rev.A 54, 1844(1996)] in the context of cavity QED. The scheme requires cavity-assisted collision processes between atoms, which cross through nonresonant cavity fields in the vacuum states. The cavity fields are only virtually excited to face the decoherence problem. That's why the requirements on the cavity quality factor can be loosened.Comment: to appear in PR

Oscillations and interactions of dark and dark-bright solitons in Bose-Einstein condensates

Solitons are among the most distinguishing fundamental excitations in a wide range of non-linear systems such as water in narrow channels, high speed optical communication, molecular biology and astrophysics. Stabilized by a balance between spreading and focusing, solitons are wavepackets, which share some exceptional generic features like form-stability and particle-like properties. Ultra-cold quantum gases represent very pure and well-controlled non-linear systems, therefore offering unique possibilities to study soliton dynamics. Here we report on the first observation of long-lived dark and dark-bright solitons with lifetimes of up to several seconds as well as their dynamics in highly stable optically trapped $^{87}$Rb Bose-Einstein condensates. In particular, our detailed studies of dark and dark-bright soliton oscillations reveal the particle-like nature of these collective excitations for the first time. In addition, we discuss the collision between these two types of solitary excitations in Bose-Einstein condensates.Comment: 9 pages, 4 figure

Label-free segmentation of co-cultured cells on a nanotopographical gradient

The function and fate of cells is influenced by many different factors, one of which is surface topography of the support culture substrate. Systematic studies of nanotopography and cell response have typically been limited to single cell types and a small set of topographical variations. Here, we show a radical expansion of experimental throughput using automated detection, measurement, and classification of co-cultured cells on a nanopillar array where feature height changes continuously from planar to 250 nm over 9 mm. Individual cells are identified and characterized by more than 200 descriptors, which are used to construct a set of rules for label-free segmentation into individual cell types. Using this approach we can achieve label-free segmentation with 84% confidence across large image data sets and suggest optimized surface parameters for nanostructuring of implant devices such as vascular stents

Gas morphology and energetics at the surface of PDRs: new insights with Herschel observations of NGC 7023

We investigate the physics and chemistry of the gas and dust in dense photon-dominated regions (PDRs), along with their dependence on the illuminating UV field. Using Herschel-HIFI observations, we study the gas energetics in NGC 7023 in relation to the morphology of this nebula. NGC 7023 is the prototype of a PDR illuminated by a B2V star and is one of the key targets of Herschel. Our approach consists in determining the energetics of the region by combining the information carried by the mid-IR spectrum (extinction by classical grains, emission from very small dust particles) with that of the main gas coolant lines. In this letter, we discuss more specifically the intensity and line profile of the 158 micron (1901 GHz) [CII] line measured by HIFI and provide information on the emitting gas. We show that both the [CII] emission and the mid-IR emission from polycyclic aromatic hydrocarbons (PAHs) arise from the regions located in the transition zone between atomic and molecular gas. Using the Meudon PDR code and a simple transfer model, we find good agreement between the calculated and observed [CII] intensities. HIFI observations of NGC 7023 provide the opportunity to constrain the energetics at the surface of PDRs. Future work will include analysis of the main coolant line [OI] and use of a new PDR model that includes PAH-related species.Comment: Accepted for publication in Astronomy and Astrophysics Letters (Herschel HIFI special issue), 5 pages, 5 figure

The Modelling of InfraRed Dark Clouds

This paper presents results from modelling 450 micron and 850 micron continuum and HCO+ line observations of three distinct cores of an infrared dark cloud (IRDC) directed toward the W51 GMC. In the sub-mm continuum these cores appear as bright, isolated emission features. One of them coincides with the peak of 8.3 micron extinction as measured by the Midcourse Space Experiment satellite. Detailed radiative transfer codes are applied to constrain the cores' physical conditions to address the key question: Do these IRDC-cores harbour luminous sources? The results of the continuum model, expressed in the $\chi^2$ quality-of-fit parameter, are also constrained by the absence of 100 micron emission from IRAS. For the sub-mm emission peaks this shows that sources of 300 solar luminosities are embedded within the cores. For the extinction peak, the combination of continuum and HCO+ line modelling indicates that a heating source is present as well. Furthermore, the line model provides constraints on the clumpiness of the medium. All three cores have similar masses of about 70-150 solar masses and similar density structures. The extinction peak differs from the other two cores by hosting a much weaker heating source, and the sub-mm emission core at the edge of the IRDC deviates from the other cores by a higher internal clumpiness.Comment: 13 pages, 13 figures, accepted for publication in A&

Disks around CQ Tau and MWC 758: dense PDR or gas dispersal?

The overall properties of disks surrounding intermediate PMS stars (HAe) are not yet well constrained by current observations. The disk inclination, which significantly affect SED modeling, is often unknown. We attempted to resolve the disks around CQ Tau and MWC 758, to provide accurate constraints on the disk parameters, in particular the temperature and surface density distribution. We report arcsecond resolution observations of dust and CO line emissions with the IRAM array. The disk properties are derived using a standard disk model. We use the Meudon PDR code to study the chemistry. The two disks share some common properties. The mean CO abundance is low despite disk temperatures above the CO condensation temperature. Furthermore, the CO surface density and dust opacity have different radial dependence. The CQ Tau disk appears warmer, and perhaps less dense than that of MWC 758. Modeling the chemistry, we find that photodissociation of CO is a viable mechanism to explain the low abundance. The photospheric flux is not sufficient for this: a strong UV excess is required. In CQ Tau, the high temperature is consistent with expectation for a PDR. The PDR model has difficulty explaining the mild temperatures obtained in MWC 758, for which a low gas-to-dust ratio is preferred. A yet unexplored alternative could be that, despite currently high gas temperatures, CO remains trapped in grains, as the models suggest that large grains can be cold enough to prevent thermal desorption of CO. The low inclination of the CQ Tau disk, ~30^\circ, challenges previous interpretations given for the UX Ori - like luminosity variations of this star. We conclude that CO cannot be used as a simple tracer of gas-to-dust ratio, the CO abundance being affected by photodissociation, and grain growth.Comment: Accepted for publication in Astronomy & Astrophysic