New opportunities in design often surface with scientific advances, however, the rapid pace of scientific findings in biological domains, and their complexity, may impede effective technological design. This paper addresses such challenges through weaving phases of scientific discovery, analytical description, and technological design in an integrative "d3 Methodology." The method is implemented using human-guided automated processes developed with cognitive-based considerations. A case study of designing myosin bio-libraries is specifically investigated, and optimization results suggest that biolibraries of designed synthetic isoforms have advantages over natural isoforms. The findings are motivating for future scientific endeavors to investigate the benefits of designed myosins, thus demonstrating reciprocity among design and science. The successes in implementing each d3 phase suggests the methodology is a feasible approach for nanoscale biosystems design, and is well-suited for driving the scientific inquiries of today towards the novel technologies of tomorrow.