Overview

Context

Biological macromolecules such as proteins and nucleic acids are inherently flexible molecules, whose function (or malfunction) critically depends on interconversions between different conformational states. Understanding how biomolecules work therefore requires a quantitative characterization of their thermally accessible conformational landscape. The task is challenging, however, because many of the populated conformers are only transiently formed and marginally populated, so that they remain invisible to most standard biophysical techniques. Over the past two decades, nuclear magnetic resonance (NMR) has emerged as an extremely powerful tool to study these elusive states at atomic resolution. Central to this success has been the development of chemical exchange-based approaches, such as (CPMG, R$_{1ρ}$) relaxation dispersion and chemical exchange saturation transfer (CEST) experiments, with the numerical tools needed to extract the kinetic (rates) and thermodynamic (populations) parameters associated with the exchange process and the structural information (chemical shifts) of the sparsely populated, "invisible" excited states.

About ChemEx

ChemEx is an open-source Python application for the analysis of NMR chemical exchange data, whose general idea is to integrate the evolution matrix of the spin-system of interest over the pulse sequence and extract the best-fit parameters by least-squares optimization. As ChemEx does not rely on analytical equations to fit the data sets, any type of experiments (e.g., D-CEST/COS-CEST) or kinetic models (e.g., 3-state exchange model) can be simulated, and most experimental details (e.g., finite pulse width, off-resonance effects, etc.) can be taken into account. ChemEx offers a wide range of pulse sequences and kinetic models to choose from. Some of its main features include multi-step fits, joint analysis of datasets from different experiments, error analysis, grid search, etc. This documentation provides an overview of these different features, along with a description of different examples illustrating their use.

ChemEx is a pure Python package, leveraging established open-source libraries like NumPy, SciPy, Matplotlib, Rich, and pydantic. The minimization process utilizes the LMFIT module, encompassing multiple optimization algorithms available in SciPy.