Energetics of Non-Covalent Interactions in Biological Systems
EMSL Project ID
30496
Abstract
Complex molecular systems typically include aggregates held together by non-covalent bonds that collectively exceed the strength of covalent bonds. Additionally, the important chemical processes of molecular recognition and self-assembly are largely governed by non-covalent interactions between molecules. Non-covalent interactions determine the enzymatic activity of proteins. The precise structure of an enzyme active site is essential for performance of its catalytic function. The substrate of an enzyme usually binds in an active site via several simultaneous non-covalent contacts. Direct inhibition of enzyme activity requires a pharmaceutical that competes with the substrate. It follows that fundamental understanding of the nature and strength of non-covalent interactions is important for rational drug design. An inordinate number of therapeutic compounds contain quaternary amines, guanidinium groups, phosphates, or aromatic rings. These are important functional groups that determine interaction of the drug with targeted biomolecules. The proposed research will focus on obtaining molecular level understanding of the formation and stability of non-covalent complexes (NCX) involving these functional groups that play a central role in a variety of biological processes.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2008-10-01
End Date
2011-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Laskin J, Z Yang, and AS Woods. 2011. "Competition between Covalent and Noncovalent Bond Cleavages in Dissociation of Phosphopeptide-Amine Complexes." Physical Chemistry Chemical Physics. PCCP 13(15):6936-6946. doi:10.1039/C1CP00029B