20,059 research outputs found
Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening
Computational techniques such as structure-based virtual screening require carefully prepared 3D models of potential small-molecule ligands. Though powerful, existing commercial programs for virtual-library preparation have restrictive and/or expensive licenses. Freely available alternatives, though often effective, do not fully account for all possible ionization, tautomeric, and ring-conformational variants. We here present Gypsum-DL, a free, robust open-source program that addresses these challenges. As input, Gypsum-DL accepts virtual compound libraries in SMILES or flat SDF formats. For each molecule in the virtual library, it enumerates appropriate ionization, tautomeric, chiral, cis/trans isomeric, and ring-conformational forms. As output, Gypsum-DL produces an SDF file containing each molecular form, with 3D coordinates assigned. To demonstrate its utility, we processed 1558 molecules taken from the NCI Diversity Set VI and 56,608 molecules taken from a Distributed Drug Discovery (D3) combinatorial virtual library. We also used 4463 high-quality protein-ligand complexes from the PDBBind database to show that Gypsum-DL processing can improve virtual-screening pose prediction. Gypsum-DL is available free of charge under the terms of the Apache License, Version 2.0
PyCUDA and PyOpenCL: A Scripting-Based Approach to GPU Run-Time Code Generation
High-performance computing has recently seen a surge of interest in
heterogeneous systems, with an emphasis on modern Graphics Processing Units
(GPUs). These devices offer tremendous potential for performance and efficiency
in important large-scale applications of computational science. However,
exploiting this potential can be challenging, as one must adapt to the
specialized and rapidly evolving computing environment currently exhibited by
GPUs. One way of addressing this challenge is to embrace better techniques and
develop tools tailored to their needs. This article presents one simple
technique, GPU run-time code generation (RTCG), along with PyCUDA and PyOpenCL,
two open-source toolkits that support this technique.
In introducing PyCUDA and PyOpenCL, this article proposes the combination of
a dynamic, high-level scripting language with the massive performance of a GPU
as a compelling two-tiered computing platform, potentially offering significant
performance and productivity advantages over conventional single-tier, static
systems. The concept of RTCG is simple and easily implemented using existing,
robust infrastructure. Nonetheless it is powerful enough to support (and
encourage) the creation of custom application-specific tools by its users. The
premise of the paper is illustrated by a wide range of examples where the
technique has been applied with considerable success.Comment: Submitted to Parallel Computing, Elsevie
PRETZEL: Opening the Black Box of Machine Learning Prediction Serving Systems
Machine Learning models are often composed of pipelines of transformations.
While this design allows to efficiently execute single model components at
training time, prediction serving has different requirements such as low
latency, high throughput and graceful performance degradation under heavy load.
Current prediction serving systems consider models as black boxes, whereby
prediction-time-specific optimizations are ignored in favor of ease of
deployment. In this paper, we present PRETZEL, a prediction serving system
introducing a novel white box architecture enabling both end-to-end and
multi-model optimizations. Using production-like model pipelines, our
experiments show that PRETZEL is able to introduce performance improvements
over different dimensions; compared to state-of-the-art approaches PRETZEL is
on average able to reduce 99th percentile latency by 5.5x while reducing memory
footprint by 25x, and increasing throughput by 4.7x.Comment: 16 pages, 14 figures, 13th USENIX Symposium on Operating Systems
Design and Implementation (OSDI), 201
Transparency in Complex Computational Systems
Scientists depend on complex computational systems that are often ineliminably opaque, to the detriment of our ability to give scientific explanations and detect artifacts. Some philosophers have s..
solveME: fast and reliable solution of nonlinear ME models.
BackgroundGenome-scale models of metabolism and macromolecular expression (ME) significantly expand the scope and predictive capabilities of constraint-based modeling. ME models present considerable computational challenges: they are much (>30 times) larger than corresponding metabolic reconstructions (M models), are multiscale, and growth maximization is a nonlinear programming (NLP) problem, mainly due to macromolecule dilution constraints.ResultsHere, we address these computational challenges. We develop a fast and numerically reliable solution method for growth maximization in ME models using a quad-precision NLP solver (Quad MINOS). Our method was up to 45 % faster than binary search for six significant digits in growth rate. We also develop a fast, quad-precision flux variability analysis that is accelerated (up to 60Ă— speedup) via solver warm-starts. Finally, we employ the tools developed to investigate growth-coupled succinate overproduction, accounting for proteome constraints.ConclusionsJust as genome-scale metabolic reconstructions have become an invaluable tool for computational and systems biologists, we anticipate that these fast and numerically reliable ME solution methods will accelerate the wide-spread adoption of ME models for researchers in these fields
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