How Simulations Reveal Dynamics, Disorder, and the Energy Landscapes of Biomolecular Function

Abstract

Over the last 40 years, the area of computational molecular biophysics has grown and developed to the point where simulations can now provide detailed mechanistic insights, suggest theoretical principles that underpin function, and provide frameworks for understanding and interpreting experimental measurements. The success of molecular simulations has been the result of the unrelenting development of novel theoretical models, exponential growth in computational resources, and advances in structural biology techniques. Through the continued refinement and application of diverse classes of models, general themes in biomolecular dynamics are beginning to surface. In particular, molecular simulations are highlighting the pervasive role that orderdisorder events play in molecular biology. These dynamic modes of function are transforming our perspective on the role that entropy has in many large‐scale biological processes.

Exploring biomolecular energy landscapes

“…Furthermore, due to the lower stability gap between native and non-native states, structure prediction as well as studies of folding mechanisms and kinetics become even more challenging for RNA. 16,17 Various experiments [18][19][20] and numerical simulations [21][22][23] have succeeded in extracting specific features of biomolecular energy landscapes. Nonetheless, determining the global topography of the landscape, and predicting or interpreting emergent properties have proved more difficult.…”