DP4-AI Automated NMR Data Analysis: Straight from Spectrometer to Structure

Abstract

<div> <p>A robust system for automatic processing and assignment of raw 13C and 1H NMR data DP4-AI has been developed and integrated into our computational organic molecule structure elucidation workflow. Starting from a molecular structure with undefined stereochemistry or other structural uncertainty, this system allows for completely automated structure elucidation. Methods for NMR peak picking using objective model selection and algorithms for matching the calculated 13C and 1H NMR shifts to peaks in noisy experimental NMR data were developed. DP4-AI achieved a 60-fold increase in processing speed, and near-elimination of the need for scientist time, when rigorously evaluated used a challenging test set of molecules. DP4-AI represents a leap forward in NMR structure elucidation and a step-change in the functionality of DP4. It enables high-throughput analyses of databases and large sets of molecules, which were previously impossible, and paves the way for the discovery of new structural information through machine learning. This new functionality has been coupled with an intuitive GUI and is available as open-source software at https://github.com/KristapsE/DP4-AI.</p> </div> <br>

Synthetic biology approaches to actinomycete strain improvement

“…Computer Assisted Structural Elucidation (CASE) approaches, both commercial and academic, have been developed as powerful tools to help in the process through the generation of prioritized structural proposals, although these applications provide only planar (2D) structures and further improvements are still required to determine 3D structures (Burns, Mazzola and Reynolds 2019 ). Moreover, the DP4-AI software has emerged as a tool complementary to CASE for completely automated 3D structural elucidation starting from raw 13 C and 1 H NMR data (Howarth, Ermanis and Goodman 2020 ). Apart from these tools, databases including calculated/real NMR data and NMR structural features easily recognizable in NMR spectra have been developed to speed up the structural elucidation of new compounds and were reviewed recently (Pérez-Victoria, Martín and Reyes 2016 ).…”

Database Independent Automated Structure Elucidation of Organic Molecules Based on IR, 1H NMR, 13C NMR, and MS Data

“…Although CASE (Computer Aided Structure Elucidation) programs are beginning to provide very good results in structure elucidation, they are still not entirely automated and usually a number of 2D in addition to the 1D NMR spectra must be provided. 29 A recently reported system for fully automatic processing and assignment of 1 H and 13 C NMR spectra, that can further elucidate and determine the relative stereochemistry of complex molecules 34 indicates that the development of structure-elucidation systems is still a lively and evolving field.…”

Real-time Prediction of 1H and 13C Chemical Shifts with DFT accuracy using a 3D Graph Neural Network

“…Ermanis and Goodman recently introduced the DP4-AI platform, which enables automated stereoisomer elucidation directly from a 1 H and 13 C spectrum. 19 In general, however, the time and computational resources associated with quantum chemical approaches can be significant, particularly for large and conformationally flexible molecules. 20 Even with access to high-performance computing resources, the consideration of multiple structures in a high-throughput manner is highly challenging at present.…”