From Atoms to Living Organisms: Emergent Complexity of Multiscale Computational Modeling

Biomolecular assemblies exhibit "emergent behavior" in both the temporal and spatial domains. As observed in long-timescale molecular dynamics simulations or in 3D models of large-scale biomolecular systems, the behavior that emerges on these scales is not only more than the sum of the (temporal or spatial) parts, but quite different and unexpected. Examples include: (1) slow conformational changes in protein folding and protein-protein binding enabled by fast motion in long molecular dynamics simulations; (2) the interpretation and refinement of intermediate-resolution electron microscopy (EM) structures using multiple or flexible atomic fragments; and (3) the segmentation of the molecular building blocks of living organisms in low-resolution data from EM or tomography. The unifying goal of our efforts is to observe and to take into account functional dynamics in the native environment (solution or vitreous ice) or in silico and then to reconstruct and interpret the 3D shapes of the conformational ensembles across multiple spatial and temporal scales. I will argue that, in the future, it may be useful to employ a "systems" perspective in biomolecular modeling whenever complex phenomena arise that cannot be predicted from isolated degrees of freedom.