Metadynamics Simulations Rationalise the Conformational Effects Induced by N-Methylation of RGD Cyclic Hexapeptides

Cristina Paissoni; Michela Ghitti; Laura Belvisi; Andrea Spitaleri; Giovanna Musco

doi:10.1002/chem.201501196

Metadynamics Simulations Rationalise the Conformational Effects Induced by N-Methylation of RGD Cyclic Hexapeptides

Cristina Paissoni, Michela Ghitti, Laura Belvisi, Andrea Spitaleri, Giovanna Musco

IRCCS Ospedale San Raffaele

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	14165-14170
Number of pages	6
Journal	Chemistry - A European Journal
Volume	21
Issue number	40
DOIs	https://doi.org/10.1002/chem.201501196
Publication status	Published - Sep 28 2015

Keywords

docking
integrin
metadynamics
methylation
peptides

ASJC Scopus subject areas

Medicine(all)

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10.1002/chem.201501196

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AU - Paissoni, Cristina

AU - Ghitti, Michela

AU - Belvisi, Laura

AU - Spitaleri, Andrea

AU - Musco, Giovanna

PY - 2015/9/28

Y1 - 2015/9/28

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AB - 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.

KW - docking

KW - integrin

KW - metadynamics

KW - methylation

KW - peptides

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Metadynamics Simulations Rationalise the Conformational Effects Induced by N-Methylation of RGD Cyclic Hexapeptides

Abstract

Keywords

ASJC Scopus subject areas

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