Protein core repacking is a standard test of protein modeling software. A recent study of six different modeling software packages showed that they are more successful at predicting side chain conformations of core compared to surface residues. All the modeling software tested have multicomponent energy functions, typically including contributions from solvation, electrostatics, hydrogen bonding and Lennard-Jones interactions in addition to statistical terms based on observed protein structures. We investigated to what extent a simplified energy function that includes only stereochemical constraints and repulsive hard-sphere interactions can correctly repack protein cores. For single residue and collective repacking, the hard-sphere model accurately recapitulates the observed side chain conformations for Ile, Leu, Phe, Thr, Trp, Tyr and Val. This result shows that there are no alternative, sterically allowed side chain conformations of core residues. Analysis of the same set of protein cores using the Rosetta software suite revealed that the hard-sphere model and Rosetta perform equally well on Ile, Leu, Phe, Thr and Val; the hard-sphere model performs better on Trp and Tyr and Rosetta performs better on Ser. We conclude that the high prediction accuracy in protein cores obtained by protein modeling software and our simplified hard-sphere approach reflects the high density of protein cores and dominance of steric repulsion.

When a gravitational wave is detected by Advanced LIGO/Virgo, sophisticated parameter estimation (PE) pipelines spring into action. These pipelines leverage approximants to generate large numbers of theoretical gravitational waveform predictions to characterize the detected signal. One of the most accurate and physically comprehensive classes of approximants in wide use is the "Spinning Effective One Body-Numerical Relativity" (SEOBNR) family. Waveform generation with these approximants can be computationally expensive, which has limited their usefulness in multiple data analysis contexts. In prior work we improved the performance of the aligned-spin approximant SEOBNR version 2 (v2) by nearly 300x. In this work we focus on optimizing the full eight-dimensional, precessing approximant SEOBNR version 3 (v3). While several v2 optimizations were implemented during its development, v3 is far too slow for use in state-of-the-art source characterization efforts for long-inspiral detections. Completion of a PE run after such a detection could take centuries to complete using v3. Here we develop and implement a host of optimizations for v3, calling the optimized approximant v3 Opt. Our optimized approximant is about 340x faster than v3, and generates waveforms that are numerically indistinguishable.

The transmission rate is a central parameter in mathematical models of infectious disease. Its pivotal role in outbreak dynamics makes estimating the current transmission rate and uncovering its dependence on relevant covariates a core challenge in epidemiological research as well as public health policy evaluation. Here, we develop a method for flexibly inferring a time‐varying transmission rate parameter, modeled as a function of covariates and a smooth Gaussian process (GP). The transmission rate model is further embedded in a hierarchy to allow information borrowing across parallel streams of regional incidence data. Crucially, the method makes use of optional vaccination data as a first step toward modeling of endemic infectious diseases. Computational techniques borrowed from the Bayesian spatial analysis literature enable fast and reliable posterior computation. Simulation studies reveal that the method recovers true covariate effects at nominal coverage levels. We analyze data from the COVID‐19 pandemic and validate forecast intervals on held‐out data. User‐friendly software is provided to enable practitioners to easily deploy the method in public health research.