The emerging role of physical modeling in the future of structure determination

Biomolecular structure determination has long relied on heuristics based on physical insight; however, recent efforts to model conformational ensembles and to make sense of sparse, ambiguous, and noisy data have revealed the value of detailed, quantitative physical models in structure determination. We review these two key challenges, describe different approaches to physical modeling in structure determination, and illustrate several successes and emerging technologies enabled by physical modeling.\n\nHighlightsO_LIQuantitative physical modeling is emerging as a key tool in structure determination\nC_LIO_LIThere are different approaches to incorporate physical modeling into structure determination\nC_LIO_LIModeling conformational ensembles and making sense of sparse, noisy, and ambiguous data are two challenges where physical modeling can play a prominent role\nC_LI