The solvent-solute interface of a biomolecule is a dynamic but yet highly structured domain that links a chemically diverse solute surface to the chemically homogeneous bulk aqueous phase. The role of the resulting intermediate domain, i.e. the "hydration shell", in regulating DNA structure and recognition has been addressed here by time-resolved infrared spectroscopy. A highly reproducible automated hydration pulse regime was established and implemented for attenuated total reflectance (ATR) Fourier transform infrared (FTIR) spectroscopy to monitor the structural response of DNA to an incremental growth of its hydration shell on its intrinsic time scale of seconds. The transition from the crystallographically defined BI to the BII substate of B-DNA was found to be driven by the increase of water disorder upon growth of the hydration shell, derived from the water OH-stretching absorption frequency and band width changes. 2D correlation analysis was used to identify different water clusters from the temporal behaviour of their water OH stretching frequencies. The results show that BII-stabilizing structural constraints are exerted by strong water-DNA H-bonds in the grooves of B-DNA and are relieved when the groove-bound water merges into a contiguous hydration shell with the less H-bonded PO2- -solvation sphere at ~14 water molecules per DNA phosphate. The H-bond imbalance at the disjunct hydration sites is split symmetrically around the average H-bond strength of bulk water. Thus, merging into a contiguous hydration shell proceeds at little enthalpic cost and homogeneous connectivity to the outer bulk-like H-bond network, such that alteration in the network distant from the DNA can regulate the BI-BII transition in a cooperative manner. The water connectivity is disrupted by DNA-binding peptides. Remarkably, the data show that the replacement of hydration shell water upon ligand biding is crucial in conferring substate specific recognition by peptides that have little intrinsic structural preference. The antibacterial peptide indolicidin secreted from bovine neutrophils dehydrates the non-PO2--bound hydration sites, thereby rendering the unstructured peptide highly specific for the BI state with vibrational signature almost identical to the bacterial minor groove binder netropsin. The proposed dominant role of hydration shell water for DNA conformation was challenged by studying the competing effect of structured water in the coordination-shell of the lanthanide Eu3+ on water structure in the DNA hydration shell. Whereas no effect is seen at low hydration, a hydrogen-like phase is formed at a stoichiometric ratio of Eu3+ :DNA:H2O of 1:10:140, characterized by a strong increase of the molar volume of hydration water. This novel phase appears attractive for lanthanide and possibly actine separation approaches based on biomolecular coordination.

Poly(2-ethyl-2-oxazoline) (PEOX) is a nonionic, synthetic polymer which is soluble in both a variety organic solvents and water. The negative entropy of mixing of this polymer in aqueous solution suggested that it adopts a rigid conformation such as a helix in aqueous solution. Hydrogen bonding between PEOX and water molecules is thought to facilitate a special conformation that is specific to aqueous solution. The intent of this work is to investigate the conformation of PEOX in aqueous solution and consequently propose the mechanism by which it would adsorb onto cellulose and make it a valuable additive in paper processing. This work ultimately contributes to the greater matter of understanding the mechanisms by which water solvates nonionic polymers. Viscometry measurements of PEOX in water show that its shape scales similar to a random coil and that its molecules collapse in the presence of sodium chloride. Investigation into the molecular structure of PEOX through molecular scale simulations have revealed that although a rigid helical conformation does not exist, the potential exists for PEOX to have secondary helical structure in both water and other solvents. Without the rigid predicted structure, however, it is not surprising that PEOX does not adsorb well on cellulose. Comparing this folded helical conformation to a random coil conformation reveals that the random coil produces a lower energy system in water.

The function of a protein is largely dictated by its natural shape called the "native conformation." Since the native conformation and the global minimum energy configuration highly correlate, predicting this conformation is a global optimization known as the "protein folding problem." It is computationally intensive due to the high-dimensional and complex energy landscape. Typical conformation algorithms combine a probabilistic search with analytical optimization. The analytical portion typically takes longer than the probabilistic part since more function evaluations are required, which are algorithm bottlenecks. To reduce the computational cost, this research studies the effects of exponential energy landscaping (XEL) on three analytical optimization algorithms: Newton's method, a quasi-Newton algorithm (QNA), and the Broyden-Fletcher-Goldfarb-Shanno (BFGS) algorithm. The XEL changes the heights and the depths of the extrema but keeps their location the same, which eliminates the troublesome process of remapping minima onto the original landscape. The Newton-XEL is found to have a similar convergence property as Newton's method by showing that their error residues are of the same order. Found by observation, stability and convergence are improved when the error residue is bounded. While XEL is found to have no effect on the similarity of resulting configurations to the native conformation, results show that the XEL can improve the speed in terms of average iterations in the QNA by 47% and in the BFGS by 41%. In terms of the average score improvement, which indicates how the energy of the resulting configuration is compared to that of the initial configuration, the XEL can improve the quality of resulting configurations in the QNA by 12% and in the BFGS by 10%. Since both results were not achieved simultaneously, the adaptive exponential energy landscaping (AXEL) is developed. The results lead to the conclusion that a trade-off between quality and speed must be considered when XEL is implemented. To improve speed by 15% to 47% and efficiency by 13% to 75%, XEL with n within 2⁻⁹-2⁻⁵ should be used and to improve quality by 4% to 7%, AXEL with Scheme E that keeps the error residue bounded should be used.

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Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.