We propose to use EMSL supercomputing resources to continue gaining a molecular level understanding on the catalytic mechanisms of monoterpene synthases (MTSs). Specifically, we will perform an extensive set of atomistic simulations to elucidate how steric and electrostatic confinement affect the conformational space of highly reactive carbocation intermediates in MTSs. Based on the previous studies supported by EMSL supercomputing resources, we will continue exploring the conformational space of reaction intermediates and find key amino acids that influence enzyme specificity and selectivity by using molecular dynamics (MD) simulations and hybrid QM/MM methods. Our computational results will be iteratively compared with the corresponding experimental results provided by our collaborator at Washington State University (WSU) to validate expected reaction paths and a role of key amino acids observed from computational approaches. This research is a key component of DOE Basic Energy Science Physical Bioscience program at PNNL.