The present invention provides methods of designing and generating polypeptide variants that have altered function compared to a parent polypeptide. The present invention further provides a computer program product for carrying out the design of a variant polypeptide. The present invention further provides nucleic acids encoding terpene cyclase variants, as well as vectors and host cells comprising the nucleic acids. The present invention further provides variant terpene cyclases; methods of producing the variant terpene cyclases; and methods of producing isoprenoid compounds.