Rise of the Allotrope Simple Model: Update from 2023 Fall Allotrope Connect.

The Allotrope Foundation (AF) started as a group of pharmaceutical companies, instrument, and software vendors that set out to simplify the exchange of data in the laboratory. After a decade of work, they released products that have found adoption in various companies. Most recently, the Allotrope Simple Model (ASM) was developed to speed up and widen the adoption. As a result, the Foundation has recently added chemical companies and, importantly, is reworking its business model to lower the entry barrier for smaller companies. Here, we present the proceedings from the Allotrope Connect Fall 2023 conference and summarize the technical and organizational developments at the Foundation since 2020.

A probabilistic view of protein stability, conformational specificity, and design.

Various approaches have used neural networks as probabilistic models for the design of protein sequences. These "inverse folding" models employ different objective functions, which come with trade-offs that have not been assessed in detail before. This study introduces probabilistic definitions of protein stability and conformational specificity and demonstrates the relationship between these chemical properties and the [Formula: see text] Boltzmann probability objective. This links the Boltzmann probability objective function to experimentally verifiable outcomes. We propose a novel sequence decoding algorithm, referred to as "BayesDesign", that leverages Bayes' Rule to maximize the [Formula: see text] objective instead of the [Formula: see text] objective common in inverse folding models. The efficacy of BayesDesign is evaluated in the context of two protein model systems, the NanoLuc enzyme and the WW structural motif. Both BayesDesign and the baseline ProteinMPNN algorithm increase the thermostability of NanoLuc and increase the conformational specificity of WW. The possible sources of error in the model are analyzed.