Molecular Dynamics Simulations to Study Structure-Function Relationship in Psychrophilic Enzymes

Abstract

The structural determinants of enzymes adapted to different temperatures are a key pre-requisite both for basic and applied research. These differences are very often related to subtle changes at the sequence- and structure-level, which are difficult to correlate with changes in protein activity and stability or even to be detected. In this scenario, molecular dynamics simulations revealed a suitable and promising approach to compare cold- and warm-adapted enzymes, especially in the last two decades. The current view suggests that different strategies can be employed by enzymes to adapt to low-temperature environments. Nevertheless, common trends can be detected either in flexibility profiles of cold-adapted enzymes or in their network of intra- and intermolecular interactions. Indeed, we need to establish a family-centered point of view to unveil the molecular mechanisms of enzyme cold adaptation. Enzymes that belong to the same family or superfamily and thus share the fold and functional sites evolved analogous structural and dynamic patterns to overcome the detrimental effects induced by low temperatures. In this chapter, we will briefly introduce the applications of molecular dynamics to the study of psychrophilic enzymes, the limits and advantages of these computational techniques, the need to complement it with experimental data, along with we will discuss the future directions that research in this field can pursue.