The article describes Foldit, a multiplayer online game designed to engage non-scientists in solving complex protein structure prediction problems. Foldit players use direct manipulation tools and user-friendly versions of the Rosetta structure prediction methodology to interact with protein structures, competing and collaborating to optimize computed energy. The game has shown that top players excel at solving challenging structure refinement problems, particularly those requiring substantial backbone rearrangements to bury hydrophobic residues. Players develop new strategies and algorithms, exploring both conformational space and search strategy space. The integration of human visual problem-solving and strategy development with computational algorithms through interactive multiplayer games is a powerful approach to solving computationally intensive scientific problems. The article also highlights the social and motivational aspects of Foldit, which enhance player engagement and motivation. Despite the promising results, there is room for improvement, especially in handling extended protein chains. The authors suggest that this hybrid human-computer optimization framework can be extended to other scientific domains where human 3D structural problem-solving can be leveraged.The article describes Foldit, a multiplayer online game designed to engage non-scientists in solving complex protein structure prediction problems. Foldit players use direct manipulation tools and user-friendly versions of the Rosetta structure prediction methodology to interact with protein structures, competing and collaborating to optimize computed energy. The game has shown that top players excel at solving challenging structure refinement problems, particularly those requiring substantial backbone rearrangements to bury hydrophobic residues. Players develop new strategies and algorithms, exploring both conformational space and search strategy space. The integration of human visual problem-solving and strategy development with computational algorithms through interactive multiplayer games is a powerful approach to solving computationally intensive scientific problems. The article also highlights the social and motivational aspects of Foldit, which enhance player engagement and motivation. Despite the promising results, there is room for improvement, especially in handling extended protein chains. The authors suggest that this hybrid human-computer optimization framework can be extended to other scientific domains where human 3D structural problem-solving can be leveraged.