Understanding the Catalytic Mechanism of Monoterpene Synthases using Atomistic Simulations
EMSL Project ID
51181
Abstract
We propose to use the EMSL supercomputing resources to gain a molecular level understanding of the catalytic mechanism of monoterpene synthases (MTSs). This research is a key component of DOE Basic Energy Science Physical Bioscience program at PNNL and it is carried out in collaboration with Prof. Lange at Washington State University (WSU). In this work, we will (1) perform an extensive set of molecular dynamics simulations of various MTSs aimed at understanding how steric and electrostatic confinement affect the conformational space of substrates and intermediates; (2) estimate the structure and energetics at the key enzymatic intermediates; (3) characterize residues that influence enzyme specificities by performing additional in-silico mutagenesis MD simulations ; and (4) iteratively compare simulation results with the corresponding experimental information provided by our experimental collaborator in order to validate a role of the specific key amino acids observed from computational approaches.
Project Details
Start Date
2019-10-01
End Date
2020-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Hoshin Kim, Narayanan Srividya, Iris Lange, Eden W. Huchala, Bojana Ginovska, B. Markus Lange, Simone Raugei. 2022. "Determinants of Selectivity for the Formation of Monocyclic and Bicyclic Products in Monoterpene Synthases." ACS Catalysis 12 (12):7453-7469. https://pubs.acs.org/doi/full/10.1021/acscatal.2c01836