ABSTRACT
Development on technology and methodology in NMR Spectroscopy has resulted in the detailed analysis and exploitation of NMR-derived geometrical information, such as NOEs (Nuclear Overhausser Enhancement), paramagnetism, relaxation times, 3 J H N H α https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9780429081385/85584ebd-a763-4dac-970a-7c0fd00ce0b6/content/eq2916.tif"/> couplings constants. These data are used as structural constrains and implemented in structure calculation through molecular dynamics protocols for the determination of 3D structures of biomolecules in solution. These structures are characterized by resolution comparable to that provided by X-ray in solid state. The main volume of information is extracted from proton-proton through space, dipolar, interaction when they are found in a distance up to 5.0-5.5 Å. The strategy of solution structure determination of biomolecules is presented below and the various stages of structural calculation using NMR derived constraints are analyzed for the case of the 36-residue synthetic peptide which represents the amino acid sequence of the Angiotensin-I Converting Enzyme catalytic site (ACE). Docking simulations are also being performed in order to set the structural basis for the ACE – substrate interaction using the Xray structure of the C-terminal ACE catalytic site and the NMR structure of the decapeptide hormone substrate, Angiotensin I.
