Structural insight into protein stability - bovine pancreatic ribonuclease A variants studies

The intermolecular bonding between molecules containing urea moieties is of interest due to the possible bidentate nature of the hydrogen bond. Experimentally, the nature of the hydrogen bond can be determined from the infra-red spectrum of thematerial. TheC=Ostretching frequency shows substantial shifts due to the additional constraints of the hydrogen bonding. To ascertain the capability of quantummechanical methods to understand better the nature of hydrogen bonds between these types of molecules, calculations on urea, dimethyl urea and their dimers have been undertaken as well as calculations of the solid state crystal structures. The calculations involve the determination of the optimum geometries and the relative energetics of the hydrogen bond formation. Calculations of the vibrational frequencies within the quasi-harmonic approximation have also been performed and some comparison can be made with experiment. In addition to a further understanding of the fundamental nature of bidentate hydrogen bond structures, a study of the cost effectiveness of various computational methodologies has been undertaken. Calculations at the Hartree-Fock, Density Functional andMP2 levels of theory are reported and a comparison of various basis sets and treatments of electron correlation is made. The calculations have provided considerable insight into the nature of these type hydrogen bonding systems. Much of the information can be used to provide more effective parameterisation of force-fields to make possible the treatment of crystal structure and crystal growth. A density functional method using the edf1 functional appears to be one of the most cost effective methods. Despite using a small basis set it provides excellent prediction of vibrational frequencies. m13.p23