2,880 research outputs found

    Spherical harmonics coeffcients for ligand-based virtual screening of cyclooxygenase inhibitors

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    Background: Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. Methodology/Principal Findings: We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. Conclusions/Significance: 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort

    Self-supervised Multi-level Face Model Learning for Monocular Reconstruction at over 250 Hz

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    The reconstruction of dense 3D models of face geometry and appearance from a single image is highly challenging and ill-posed. To constrain the problem, many approaches rely on strong priors, such as parametric face models learned from limited 3D scan data. However, prior models restrict generalization of the true diversity in facial geometry, skin reflectance and illumination. To alleviate this problem, we present the first approach that jointly learns 1) a regressor for face shape, expression, reflectance and illumination on the basis of 2) a concurrently learned parametric face model. Our multi-level face model combines the advantage of 3D Morphable Models for regularization with the out-of-space generalization of a learned corrective space. We train end-to-end on in-the-wild images without dense annotations by fusing a convolutional encoder with a differentiable expert-designed renderer and a self-supervised training loss, both defined at multiple detail levels. Our approach compares favorably to the state-of-the-art in terms of reconstruction quality, better generalizes to real world faces, and runs at over 250 Hz.Comment: CVPR 2018 (Oral). Project webpage: https://gvv.mpi-inf.mpg.de/projects/FML
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