Molecular recognition at protein surface in solution and gas phase: Five VEGF peptidic ligands show inverse affinity when studied by NMR and CID‐MS

Protein-protein interactions comprise of collection of molecular recognition events that take place at protein surfaces. A better understanding of the mechanism behind these interactions would provide deeper insight into the nature of many diseases, caused by the malfunction of protein networks, and contribute to design of molecules for efficient modulating of these interactions. One major factor in molecular recognition mechanism is interaction of reacting species with aqueous media. Thus, comparative study of noncovalent complex behavior in solution and gas phase can provide valuable information about the role of the solvent. Here examined interactions of vascular endothelial growth factor (VEGF) protein with five peptidic ligands of the same molecular weight but with different affinities. Interactions of VEGF with ligands in solution were studied by ITC and NMR, and KDs were determined. Gas phase stability was addressed using CID-MS approach. The energy transfer model was taken and adapted for the calculation of binding energy. Peptides were ranked on the basis of both solution and gas phase affinity to VEGF. The results indicate that the ranking of peptides in terms of affinity in solution is reversed compared with the gas phase ranking. This observation opens up a vast field for the future study of the system, and the determination and characterization of factors, responsible for the change of stability of noncovalent protein-ligand complexes upon complete or partial removal of the solvent. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 689–700, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com