Enzyme Dynamics: Looking Beyond a Single Structure

Conventional understanding of how enzymes function strongly emphasizes the role of structure. However, increasing evidence clearly indicates that enzymes do not remain fixed or operate exclusively in or close to their native structure. Different parts of the enzyme (from individual residues to full domains) undergo concerted motions on a wide range of time‐scales, including that of the catalyzed reaction. Information obtained on these internal motions and conformational fluctuations has so far uncovered and explained many aspects of enzyme mechanisms, which could not have been understood from a single structure alone. Although there is wide interest in understanding enzyme dynamics and its role in catalysis, several challenges remain. In addition to technical difficulties, the vast majority of investigations are performed in dilute aqueous solutions, where conditions are significantly different than the cellular milieu where a large number of enzymes operate. In this review, we discuss recent developments, several challenges as well as opportunities related to this topic. The benefits of considering dynamics as an integral part of the enzyme function can also enable new means of biocatalysis, engineering enzymes for industrial and medicinal applications. Enzyme catalysis: Last two decades have seen intense debate about the role of protein dynamics in enzyme catalysis. Evidence from a wide variety of techniques and for an increasing number of enzyme complexes has already been collected, and a better picture has emerged about how internal motions and conformational fluctuations are important contributors to the catalytic efficiency of enzymes. This review discusses new opportunities in fundamental understanding of biocatalysis as well as enzyme engineering and applications.