Theoretical and computational approaches to novel noncovalent interactions in protein structure

The first part (chapters 2--5) of this thesis characterizes aromatic-amide interactions in proteins using both systematic ab initio molecular orbital calculations on model complexes and data retrieval analyses of X-ray protein structures. The results indicate that the aromatic-amide interaction can achieve a significant stabilization energy of up to 4.0 kcal/mol. The interaction involves the entirety of the amide group. Both electrostatic and dispersion interactions are crucial to the total interaction energy. A significant stabilization energy can be achieved over a wide configurational space. Such interactions commonly occur in protein and are significant to protein structures. This part also studies the conformational characteristics of phenylalanine residues in the protein environment. Data retrieval analyses demonstrate that the conformation of phenylalanine residues in a polypeptide structure is not arbitrary but falls into three regular types. Data retrieval analyses show that 96.2% of phenylalanine residues involve one or two aromatic-amide interactions. Such an interaction is one of the important factors responsible for the conformational regularity of phenylalanine in proteins.; The second part (chapter 6) concerns the aromatic-hydrosulfide pi hydrogen bonding, phenylalanine-cysteine, and phenylalanine-cystine interactions. The aromatic-hydrosulfide pi hydrogen bonding interaction can achieve a stabilization energy of 2.60 kcal/mol. The phenylalanine-cysteine interaction denotes the interaction between the side-chains of phenylalanine and cysteine residues. Such an interaction is characterized as the phenyl-(HSCH2-) interaction. In proteins, this interaction occurs primarily in terms of the aromatic-sulfur attraction which can achieve a stabilization energy of 1.2 kcal/mol. The phenylalanine-cystine interaction is referred to as the interaction between the side-chain of phenylalanine and the cystine, which is characterized as the phenyl-(-CH2SSCH 2-) interaction. Such interactions occurring in proteins are comprised of one or two aromatic-sulfur attractions and correspond to a stabilization energy of up to 1.6 kcal/mol.; In Chapter 7, the applicability of the CHARMm force field to the interactions involving aromatic groups is analyzed. The existing CHARMm force field is suitable for aromatic-aliphatic and aromatic-amide interactions. To improve its behavior on the aromatic-aromatic, aromatic-thiol, aromatic-amine, and aromatic-alcohol interactions, new parameters are obtained through fitting the CHARMm interaction potential energy surfaces to the MP2 ones for these interactions.