11 research outputs found
Explainability in Graph Neural Networks: A Taxonomic Survey
Deep learning methods are achieving ever-increasing performance on many
artificial intelligence tasks. A major limitation of deep models is that they
are not amenable to interpretability. This limitation can be circumvented by
developing post hoc techniques to explain the predictions, giving rise to the
area of explainability. Recently, explainability of deep models on images and
texts has achieved significant progress. In the area of graph data, graph
neural networks (GNNs) and their explainability are experiencing rapid
developments. However, there is neither a unified treatment of GNN
explainability methods, nor a standard benchmark and testbed for evaluations.
In this survey, we provide a unified and taxonomic view of current GNN
explainability methods. Our unified and taxonomic treatments of this subject
shed lights on the commonalities and differences of existing methods and set
the stage for further methodological developments. To facilitate evaluations,
we generate a set of benchmark graph datasets specifically for GNN
explainability. We summarize current datasets and metrics for evaluating GNN
explainability. Altogether, this work provides a unified methodological
treatment of GNN explainability and a standardized testbed for evaluations
Joint Learning of Label and Environment Causal Independence for Graph Out-of-Distribution Generalization
We tackle the problem of graph out-of-distribution (OOD) generalization.
Existing graph OOD algorithms either rely on restricted assumptions or fail to
exploit environment information in training data. In this work, we propose to
simultaneously incorporate label and environment causal independence (LECI) to
fully make use of label and environment information, thereby addressing the
challenges faced by prior methods on identifying causal and invariant
subgraphs. We further develop an adversarial training strategy to jointly
optimize these two properties for casual subgraph discovery with theoretical
guarantees. Extensive experiments and analysis show that LECI significantly
outperforms prior methods on both synthetic and real-world datasets,
establishing LECI as a practical and effective solution for graph OOD
generalization
Artificial Intelligence for Science in Quantum, Atomistic, and Continuum Systems
Advances in artificial intelligence (AI) are fueling a new paradigm of
discoveries in natural sciences. Today, AI has started to advance natural
sciences by improving, accelerating, and enabling our understanding of natural
phenomena at a wide range of spatial and temporal scales, giving rise to a new
area of research known as AI for science (AI4Science). Being an emerging
research paradigm, AI4Science is unique in that it is an enormous and highly
interdisciplinary area. Thus, a unified and technical treatment of this field
is needed yet challenging. This work aims to provide a technically thorough
account of a subarea of AI4Science; namely, AI for quantum, atomistic, and
continuum systems. These areas aim at understanding the physical world from the
subatomic (wavefunctions and electron density), atomic (molecules, proteins,
materials, and interactions), to macro (fluids, climate, and subsurface) scales
and form an important subarea of AI4Science. A unique advantage of focusing on
these areas is that they largely share a common set of challenges, thereby
allowing a unified and foundational treatment. A key common challenge is how to
capture physics first principles, especially symmetries, in natural systems by
deep learning methods. We provide an in-depth yet intuitive account of
techniques to achieve equivariance to symmetry transformations. We also discuss
other common technical challenges, including explainability,
out-of-distribution generalization, knowledge transfer with foundation and
large language models, and uncertainty quantification. To facilitate learning
and education, we provide categorized lists of resources that we found to be
useful. We strive to be thorough and unified and hope this initial effort may
trigger more community interests and efforts to further advance AI4Science
Folded Conformation, Cyclic Pentamer, Nanostructure, and PAD4 Binding Mode of YW3-56
The physical and chemical mechanisms
of small molecules with pharmacological activity forming nanostructures
are developing into a new field of nanomedicine. By using ROESY 2D
NMR spectroscopy, tandem mass spectroscopy, transmission electron
microscopy, and computer-assisted molecular modeling, this paper demonstrates
the contribution of the folded conformation, the intra- and intermolecular
π–π stacking, the intra- and intermolecular hydrogen
bonds, and the receptor binding free energy of 6-dimethylaminonaph-2-yl-{<i>N</i>-<i>S</i>-[1-benzylcarba-moyl-4-(2-chloroacetamidobutyl)]-carboxamide
(YW3-56) to the rapid formation of nanorings and the slow formation
of nanocapsules. Thus we have developed a strategy that makes it possible
to elucidate the physical and chemical mechanisms of bioactive small
molecules forming nanostructures
Structure-Based Design of Tropane Derivatives as a Novel Series of CCR5 Antagonists with Broad-Spectrum Anti-HIV‑1 Activities and Improved Oral Bioavailability
Blocking
the entry of an HIV-1 targeting CCR5 coreceptor has emerged
as an attractive strategy to develop HIV therapeutics. Maraviroc is
the only CCR5 antagonist approved by FDA; however, serious side effects
limited its clinical use. Herein, 21 novel tropane derivatives (6–26) were designed and synthesized based on the CCR5-maraviroc
complex structure. Among them, compounds 25 and 26 had comparable activity to maraviroc and presented more
potent inhibitory activity against a series of HIV-1 strains. In addition,
compound 26 exhibited synergistic or additive antiviral
effects in combination with other antiretroviral agents. Compared
to maraviroc, both 25 and 26 displayed higher Cmax and AUC0–∞ and
improved oral bioavailability in SD rats. In addition, compounds 25 and 26 showed no significant CYP450 inhibition
and showed a novel binding mode with CCR5 different from that of maraviroc-CCR5.
In summary, compounds 25 and 26 are promising
drug candidates for the treatment of HIV-1 infection
Structure-Based Design of Tropane Derivatives as a Novel Series of CCR5 Antagonists with Broad-Spectrum Anti-HIV‑1 Activities and Improved Oral Bioavailability
Blocking
the entry of an HIV-1 targeting CCR5 coreceptor has emerged
as an attractive strategy to develop HIV therapeutics. Maraviroc is
the only CCR5 antagonist approved by FDA; however, serious side effects
limited its clinical use. Herein, 21 novel tropane derivatives (6–26) were designed and synthesized based on the CCR5-maraviroc
complex structure. Among them, compounds 25 and 26 had comparable activity to maraviroc and presented more
potent inhibitory activity against a series of HIV-1 strains. In addition,
compound 26 exhibited synergistic or additive antiviral
effects in combination with other antiretroviral agents. Compared
to maraviroc, both 25 and 26 displayed higher Cmax and AUC0–∞ and
improved oral bioavailability in SD rats. In addition, compounds 25 and 26 showed no significant CYP450 inhibition
and showed a novel binding mode with CCR5 different from that of maraviroc-CCR5.
In summary, compounds 25 and 26 are promising
drug candidates for the treatment of HIV-1 infection
Structure-Based Design of Tropane Derivatives as a Novel Series of CCR5 Antagonists with Broad-Spectrum Anti-HIV‑1 Activities and Improved Oral Bioavailability
Blocking
the entry of an HIV-1 targeting CCR5 coreceptor has emerged
as an attractive strategy to develop HIV therapeutics. Maraviroc is
the only CCR5 antagonist approved by FDA; however, serious side effects
limited its clinical use. Herein, 21 novel tropane derivatives (6–26) were designed and synthesized based on the CCR5-maraviroc
complex structure. Among them, compounds 25 and 26 had comparable activity to maraviroc and presented more
potent inhibitory activity against a series of HIV-1 strains. In addition,
compound 26 exhibited synergistic or additive antiviral
effects in combination with other antiretroviral agents. Compared
to maraviroc, both 25 and 26 displayed higher Cmax and AUC0–∞ and
improved oral bioavailability in SD rats. In addition, compounds 25 and 26 showed no significant CYP450 inhibition
and showed a novel binding mode with CCR5 different from that of maraviroc-CCR5.
In summary, compounds 25 and 26 are promising
drug candidates for the treatment of HIV-1 infection