A Variant on the CREST iMTD Algorithm for Non-Covalent Clusters of Flexible Molecules

Conformational ensemble generation and the search for the global minimum conformation are important problems in computational chemistry. In this work, a variant on the Conformer-Rotamer Ensemble Sampling Tool (CREST) iterative metadynamics (iMTD) algorithm designed for determining structural ensembles and energetics of non-covalent clusters of flexible molecules is presented. We term this new algorithm a Low-Energy Diversity-Enhanced variant on CREST, or LEDE-CREST. As with CREST, the energies are evaluated using the semiempirical GFN2-xTB extended tight binding approach. The utility of the algorithm is highlighted by generating ensembles for a variety of non-covalent clusters of flexible or rigid monomers using both CREST and LEDE-CREST