A general method for designing proteins with high conformational specificity is desirable for a variety of applications – for enzyme design, for drug target redesign, and for understanding prion-related disease. To assess the ability of algorithms to design for conformational specificity, we introduce a benchmark dataset of 200 conformational specificity design challenges. We also introduce CSDesign, an algorithm for designing proteins with high preference for a target conformation over an alternate conformation. CSDesign designs protein sequences that are predicted to prefer the target conformation with statistical significance. We apply this method \textit{in vitro} to redesign human MAP kinase ERK2, an enzyme with active and inactive conformations. Out of two designs for the active conformation, one increased activity sufficiently to retain activity in the absence of activating phosphorylations, a property not present in the wild type protein.