In Silico Study of Global Structure of Human Serum Albumin

ABSTRACT

Using a molecular dynamics (MD) method, the structural changes of albumin with temperature in the presence of salts provide mechanistic insights about the structural changes and deterministic factors that participate in albumin denaturation. These studies may be helpful in understanding the mechanism by which albumin helps the body in controlling its temperature against threatening elevations. However, there are miscellaneous reports studying the effect of temperature and denaturant surfactants on albumin structure using experimental techniques—for example, Circular Dichroism (CD) and Differential Scanning Calorimetry (DSC)—in addition to theoretical studies such as in silico experiments performed using techniques such as MD. In the present work, GROMACS software was used to study albumin simulation under different conditions. The simulation was carried out for 2 ns at 310 and 313 K in a dodecahedral box filled with simple point charge (SPC) water. The results obtained through various parameter analyses—that is, root mean square deviation (RMSD), R_g , volume, hydrogen bonding, and solubility—showed that in pure water the RMSD changes in protein backbone started from 0.18 nm and at 1000 ps grown up to 0.21 nm. Following this, there was little change to 0.27 nm. At 313 K the RMSD changes were greater, starting from 0.2 nm and until 1200 ps increased to 0.28 nm. The radius of gyration fluctuated at around 2.64 nm. This reflected only slight changes at 310 K in pure water. Analysis of the volume changes showed that the volume increased with increasing temperature. In salt solution, both R_g and the volume increased with an increase in temperature. However, at both temperatures the volume was reduced, which can lead to a reduction in osmotic pressure. A reduction in osmotic pressure under fever conditions can lead to an increment in urine volume, which is beneficial in fever conditions.

KEYWORDS:

• in silico
• human serum albumin
• molecular dynamics simulation

Acknowledgments

The financial support of Shahid Chamran University of Ahwaz and Khouzestan Science and Research Unit, Azad Islamic University, Ahvaz, Iran, is acknowledged.

Notes

Any protein in protein data bank has been identified with a unique identification code called PDB ID.

Number of molecules, pressure and temperature are constant.