Molecular dynamics studies of water and biomolecules

This thesis concerns different areas of molecular dynamics (MD) simulations. In the first part of the thesis the ability of liquid water models to mimic the real bulk water properties and the accuracy of the methods to calculate the properties of water from MD simulations were examined. There are five commonly water models, which are used when biological molecules such as peptides and proteins are simulated. The characteristic bulk water structure and dynamics of all these water models were determined and compared to experimental data.

In the second part of the thesis different methods commonly used in molecular dynamics simulations to treat the nonbonded interactions and to control the system temperature were examined. The effects of these methods on the results from molecular dynamics simulations were analyzed. Further the effect of the system size on the structure and dynamics of bulk water were also studied.

In the third part of the thesis the water model effects on structural and dynamic properties of tryptophan and the Ala-Pro dipeptide in the water were examined. The hydration, rotational reorientation and translational diffusion of the solute were to different degrees depending on the water model. The rotational reorientation and translational diffusion of the solute were found to depend on the viscosity of the water models. The confomational space of the AlaPro dipeptide in water was not affected by the water model.

In the last part of the thesis molecular dynamics simulations of cyclophilin A when free and complexed with the Ala-Pro dipeptide in water were performed. The hydration of cyclophilin A was calculated and the binding pocket of the Ala-Pro dipeptide was examined more carefully. The water structure in the binding pocket was found to mimic the experimentally obtained binding conformation of the Ala-Pro dipeptide, namely the cis conformation. This knowledge can be important for drug design.

This thesis main purpose was to examine the effects of water models on the molecular dynamics simulations results and understand the limitations and the accuracy level of the calculated properties from MD simulations. This thesis also shows the importance of the hydration when the biomolecules behaviour in the water are examined.

List of scientific papers

I. Mark P, Nilsson L (2001). Structure and dynamics of the TIP3P, SPC and SPC/E water models at 298 K. J Phys Chem A. 105: 9954-60.

II. Mark P, Nilsson L (2002). Structure and dynamics of liquid water with different long-range interaction truncation and temperature control methods in molecular dynamics simulations. J Comp Chem. [Accepted]

III. Mark P, Nilsson L (2002). A molecular dynamics study of tryptophan in water. [Submitted]

IV. Mark P, Nilsson L (2001). Molecular dynamics simulations of the ala-pro dipeptide in water: Conformational dynamics of trans and cis isomers using different water models. J Phys Chem B. 105: 8028-35.

V. Mark P, Nilsson L (2002). A molecular dynamics study of cyclophilin A when free and in complex with Ala-Pro dipetide in water. [Manuscript]