title: Catalytic control in terpenoid cyclases: multiscale modeling of thermodynamic, kinetic, and dynamic effects.
abstract: In this Opinion we review some of the key work on terpene biosynthesis using multi-scale simulation approaches. Terpene synthases generate terpenes employing beautiful and rich carbocation chemistry, including highly specific ring formations, hydride, proton, methyl, and methylene migrations, followed by reaction quenching. In spite of the chemical finesse of these enzymes, terpene synthases are highly promiscuous. Incidentally, these mischievous enzymes are very challenging to treat computationally due to the inherent complexity of the potential energy surface in carbocations and the lack of directional hydrogen bonds to active site residues. Thus, a carefully designed computational platform must be employed. Herein, we review multi-scale simulations of squalene-hopene, aristolochene, and bornyl diphosphate synthases, and highlight what we have learned from this work.
authors.affiliation: Department of Chemistry and the Lise Meitner-Minerva Center of Computational Quantum Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel. Electronic address: majort@biu.ac.il.
authors.forename: Dan Thomas
authors.initials: DT
authors.lastname: Major
authors.affiliation: Department of Chemistry and the Lise Meitner-Minerva Center of Computational Quantum Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Yehoshua
authors.initials: Y
authors.lastname: Freud
authors.affiliation: Department of Chemistry and the Lise Meitner-Minerva Center of Computational Quantum Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Weitman
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D055162:Biocatalysis; D007700:Kinetics; D008954:Models, Biological; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D019883:Alkyl and Aryl Transferases; C108877:terpene synthase