Restricted dynamics of water around a protein–carbohydrate complex: Computer simulation studies

Abstract

Water-mediated protein-carbohydrate interaction is a complex phenomenon responsible for different biological processes in cellular environment. One of the unexplored but important issues in this area is the role played by water during the recognition process and also in controlling the microscopic properties of the complex. In this study, we have carried out atomistic molecular dynamics simulations of a protein-carbohydrate complex formed between the hyaluronan binding domain of the murine Cd44 protein and the octasaccharide hyaluronan in explicit water. Efforts have been made to explore the heterogeneous influence of the complex on the dynamic properties of water present in different regions around it. It is revealed from our analyses that the heterogeneous dynamics of water around the complex are coupled with differential time scales of formation and breaking of hydrogen bonds at the interface. Presence of a highly rigid thin layer of motionally restricted water molecules bridging the protein and the carbohydrate in the common region of the complex has been identified. Such water molecules are expected to play a crucial role in controlling properties of the complex. Importantly, it is demonstrated that the formation of the protein-carbohydrate complex affects the transverse and longitudinal degrees of freedom of the interfacial water molecules in a heterogeneous manner.

Dynamics transitions at the outer vestibule of the KcsA potassium channel during gating

“…It has been shown that heterogeneity in the dynamics of water interactions is coupled to differential time scales of hydrogen bond formation and breaking (42). Using a wavelength-selective fluorescence approach (REES), we showed that entry to the inactivated state is associated with the presence of restricted/bound water molecules in the outer vestibule of KcsA (Fig.…”

Revealing the Mechanisms of Protein Disorder and N-Glycosylation in CD44-Hyaluronan Binding Using Molecular Simulation

“…Given these differences, further investigation is warranted to achieve a comprehensive consistent view. Finally, while outside the scope of this review, there have been substantial efforts using MD simulations to understand the importance of water molecules and of biomolecular conformational entropy changes in HABD binding with HA (52, 53). Findings from these simulations that can inform development of small-molecule modulators of CD44 function include reduced translational and rotational freedom of water molecules in contact with HABD and HA, and loss of HA flexibility associated with binding to HABD.…”

“…(49–51) This article reviews the contribution MD simulations have made toward developing answers to these questions. We note that others have also recently applied MD simulation to the study of CD44 HABD, with topics including conformational flexibility and the microscopic structure and dynamics of water surrounding HABD (52, 53), and the mechanism and thermodynamics of the ordered to partially disordered transition (54). …”

Insights into hydrogen bond dynamics at the interface of the charged monolayer-protected Au nanoparticle from molecular dynamics simulation

“…[28][29][30][32][33][34][35][36][37][38][39][40][41][42] Especially, the existence of polar groups at the interface can dominate the formation and breaking of interfacial HBs. 33,36,37,40 Balasubramanian and Bagchi 34 have shown that the HB lifetime between water molecules and the polar head groups (cesium pentadecafluorooctanoate) at a micelle surface is found to be much longer than that of water molecules themselves.…”