This dissertation is divided into two sections. The first section focuses on the theoretical studies of substituent effects on the thermal stabilities of collagen and collagen-like peptides, and the design of collagen-based biomaterials, including chapters 1-4. Our results reveal that electrostatic interactions play important roles in the substituent effects on the thermal stability of collagen and collagen-like peptides. Other factors, such as the intrinsic conformational preference of the monomer residues, interchain N-H⋅⋅⋅O=C and C_α-H⋅⋅⋅O=C hydrogen bonds, attractive van der Waals interactions and favorable hydrophobic effects between nonpolar side chains of the residues in adjacent chains, also contribute much to the stabilities of the triple helical structures. The results led us t...[ Read more ]

This dissertation is divided into two sections. The first section focuses on the theoretical studies of substituent effects on the thermal stabilities of collagen and collagen-like peptides, and the design of collagen-based biomaterials, including chapters 1-4. Our results reveal that electrostatic interactions play important roles in the substituent effects on the thermal stability of collagen and collagen-like peptides. Other factors, such as the intrinsic conformational preference of the monomer residues, interchain N-H⋅⋅⋅O=C and C_α-H⋅⋅⋅O=C hydrogen bonds, attractive van der Waals interactions and favorable hydrophobic effects between nonpolar side chains of the residues in adjacent chains, also contribute much to the stabilities of the triple helical structures. The results led us to predict that thioproline is a good unnatural surrogate of proline to be incorporated into collagen-based triple helical structures to achieve high thermal stability and proteolytic stability. The second section that covers chapter 5-7 focuses on the studies of the dynamic properties of the envelope glycoprotein gp120 of HIV-1 upon CD4 binding and the related biological functions. It also includes the studies of inhibiting mechanism of a new type HIV-1 entry inhibitor BMS-378806, and drug design based on this template. The MD results indicate that the binding of gp120 to CD4 has several biological implications including the stabilization of the V1/V2 stem, the reorientation of the V3 loop, and the enhancement of the rigidity of the V3 loop. All these facilitate the subsequent binding of gp120 with chemokine coreceptors. Docking studies rationalize the two different inhibiting mechanisms of BMS-378806. The designed compounds show encouraging anti-HIV activity and serve as a good starting point for the further development of new potent HIV-1 entry inhibitors.