CREMP: Conformer-rotamer ensembles of macrocyclic peptides for machine learning
This resource addresses a bottleneck in computational peptide design for therapeutic development, though it is incremental as it builds on existing tools like CREST.
The authors tackled the lack of accurate, fast, and scalable methods for modeling macrocyclic peptide conformations by introducing CREMP, a dataset containing 36,198 unique peptides with nearly 31.3 million geometries and energies, along with 3,258 macrocycles with permeability data.
Computational and machine learning approaches to model the conformational landscape of macrocyclic peptides have the potential to enable rational design and optimization. However, accurate, fast, and scalable methods for modeling macrocycle geometries remain elusive. Recent deep learning approaches have significantly accelerated protein structure prediction and the generation of small-molecule conformational ensembles, yet similar progress has not been made for macrocyclic peptides due to their unique properties. Here, we introduce CREMP, a resource generated for the rapid development and evaluation of machine learning models for macrocyclic peptides. CREMP contains 36,198 unique macrocyclic peptides and their high-quality structural ensembles generated using the Conformer-Rotamer Ensemble Sampling Tool (CREST). Altogether, this new dataset contains nearly 31.3 million unique macrocycle geometries, each annotated with energies derived from semi-empirical extended tight-binding (xTB) DFT calculations. Additionally, we include 3,258 macrocycles with reported passive permeability data to couple conformational ensembles to experiment. We anticipate that this dataset will enable the development of machine learning models that can improve peptide design and optimization for novel therapeutics.