Metadynamics Simulations Rationalise the Conformational Effects Induced by N‐Methylation of RGD Cyclic Hexapeptides1. Issue 40 (6th August 2015)

• Record Type: Journal Article
• Authors: Paissoni, Cristina; Ghitti, Michela; Belvisi, Laura; Spitaleri, Andrea; Musco, Giovanna
• Is Part Of: Chemistry. Volume 21:Issue 40(2015)
• Page Start: 14165
• Page End: 14170
• Publication Date: 2015-08-06
• Subjects: docking -- integrin -- metadynamics -- methylation -- peptides; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201501196
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: We combined metadynamics, docking and molecular mechanics/generalised born surface area (MM/GBSA) re‐scoring methods to investigate the impact of single and multiple N ‐methylation on a set of RGD cyclopeptides displaying different affinity for integrin αIIbβ3. We rationalised the conformational effects induced by N ‐methylation and its interplay with receptor affinity, obtaining good agreement with experimental data. This approach can be exploited before entering time‐consuming and expensive synthesis and binding experiments. Abstract : Saving time and money : Cyclic peptides are a promising class of molecules able to inhibit protein–protein interactions. Their application is limited due to the difficulties in predicting their 3D structure and the effects induced by chemical modifications. Metadynamics samples the conformations of a set of cyclopeptides and allows for rationalising methylation‐induced effects (see figure, CV=collective variable).