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Towards the online computer-aided design of catalytic pockets

Abstract

The engineering of catalysts with desirable properties can be accelerated by computer-aided design. To achieve this aim, features of molecular catalysts can be condensed into numerical descriptors that can then be used to correlate reactivity and structure. Based on such descriptors, we have introduced topographic steric maps that provide a three-dimensional image of the catalytic pocket—the region of the catalyst where the substrate binds and reacts—enabling it to be visualized and also reshaped by changing various parameters. These topographic steric maps, especially when used in conjunction with density functional theory calculations, enable catalyst structural modifications to be explored quickly, making the online design of new catalysts accessible to the wide chemical community. In this Perspective, we discuss the application of topographic steric maps either to rationalize the behaviour of known catalysts—from synthetic molecular species to metalloenzymes—or to design improved catalysts.

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Fig. 1: Catalytic pocket in enzymes and synthetic catalysts.
Fig. 2: Schematic representation of descriptors used in catalysis.
Fig. 3: Topographic steric maps of transition metal complexes.
Fig. 4: Application of topographic steric maps in catalyst design.
Fig. 5: Rh-catalysed asymmetric addition of phenylboronic acid to 2-cyclohexenone.
Fig. 6: Steric maps of the catalytic pocket of metalloproteins.

Code availability

The source code calculating buried volumes and steric maps is downloadable from the SambVca 2.1 web server, https://www.molnac.unisa.it/OMtools/sambvca2.1/index.html.

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Acknowledgements

L.C. thanks the King Abdullah University of Science and Technology (KAUST). This research used resources of the Core Labs and of the KAUST Supercomputing Laboratory. A.P. is a Serra Húnter fellow and thanks the Spanish MICINN for the project PGC2018-097722-B-I00. R.O. thanks University Parthenope ‘Finanziamento per il Sostegno alla Ricerca Individuale di Ateneo – Annualità 2017’ for funding.

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L.C. conceived and designed the project. L.F. and A.P. provided the DFT calculations and the buried volume and steric maps analyses. Z.C. wrote the SambVca source code. R.O. provided the analysis of the biomolecules. A.P., L.S. and V.S designed and implemented the SambVca web application. All authors contributed to the discussion, L.C. and R.O. wrote the manuscript and all authors commented on the manuscript.

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Correspondence to Luigi Cavallo.

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Falivene, L., Cao, Z., Petta, A. et al. Towards the online computer-aided design of catalytic pockets. Nat. Chem. 11, 872–879 (2019). https://doi.org/10.1038/s41557-019-0319-5

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