Utilizing Low-Dimensional Molecular Embeddings for Rapid Chemical Similarity Search.

Nearest neighbor-based similarity searching is a common task in chemistry, with notable use cases in drug discovery. Yet, some of the most commonly used approaches for this task still leverage a brute-force approach. In practice this can be computationally costly and overly time-consuming, due in part to the sheer size of modern chemical databases.

Pharmacokinetics Profiler (PhaKinPro): Model Development, Validation, and Implementation as a Web Tool for Triaging Compounds with Undesired Pharmacokinetics Profiles.

Computational models that predict pharmacokinetic properties are critical to deprioritize drug candidates that emerge as hits in high-throughput screening campaigns. We collected, curated, and integrated a database of compounds tested in 12 major end points comprising over 10,000 unique molecules. We then employed these data to build and validate binary quantitative structure-activity relationship (QSAR) models.

HIt Discovery using docking ENriched by GEnerative Modeling (HIDDEN GEM): A novel computational workflow for accelerated virtual screening of ultra-large chemical libraries.

Recent rapid expansion of make-on-demand, purchasable, chemical libraries comprising dozens of billions or even trillions of molecules has challenged the efficient application of traditional structure-based virtual screening methods that rely on molecular docking. We present a novel computational methodology termed HIDDEN GEM (HIt Discovery using Docking ENriched by GEnerative Modeling) that greatly accelerates virtual screening. This workflow uniquely integrates machine learning, generative chemistry, massive chemical similarity searching and molecular docking of small, selected libraries in the beginning and the end of the workflow.

Constraining de Sitter Space in String Theory.

We argue that the heterotic string does not have classical vacua corresponding to de Sitter space-times of dimension four or higher. The same conclusion applies to type II vacua in the absence of Ramond-Ramond fluxes. Our argument extends prior supergravity no-go results to regimes of high curvature.