Molecular Dynamics Applications to GPCR Ligand Design

Andrea Bortolato; Francesca Deflorian; Giuseppe Deganutti; Davide Sabbadin; Stefano Moro; Jonathan S. Mason

doi:10.1002/9783527806836.ch9

Molecular Dynamics Applications to GPCR Ligand Design

Andrea Bortolato, Francesca Deflorian, Giuseppe Deganutti, Davide Sabbadin, Stefano Moro, Jonathan S. Mason

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

Abstract

G protein–coupled receptors (GPCRs) represent a superfamily of receptors linked to a wide range of human diseases. The increasing number of X-ray diffraction crystal structures now available provides a solid foundation to understand the nature of key protein–ligand interactions at the final stage of the mutual recognition process. They enable structure-based drug design (SBDD), and are an important starting point for computer-aided biophysical investigations, including molecular dynamics (MD) simulations.

Recently, MD-based approaches have been successfully applied to understand ligand–GPCR binding at a molecular level. Promising approaches and case studies of MD methods applied to SBDD include (i) analysis of locations and thermodynamic properties of water molecules; (ii) ligand-binding free energy predictions; (iii) ligand-binding event and kinetics evaluations.

Original language	English
Title of host publication	Biomolecular Simulations in Structure‐Based Drug Discovery
Editors	Francesco L. Gervasio, Vojtech Spiwok
Publisher	Wiley
Chapter	9
Pages	225-246
Number of pages	22
ISBN (Electronic)	9783527806836
ISBN (Print)	9783527342655
DOIs	https://doi.org/10.1002/9783527806836.ch9
Publication status	Published - 10 Dec 2018
Externally published	Yes

Publication series

Name	Methods and Principles in Medicinal Chemistry
Publisher	Wiley
ISSN (Electronic)	1865-0562

Bibliographical note

Keywords

ABMD
GPCR ligand design
ligand-receptor binding
molecular dynamics simulations
protein-ligand binding free energy
SBDD
water molecule-mediated interactions

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/9783527806836.ch9

Cite this

Molecular Dynamics Applications to GPCR Ligand Design. / Bortolato, Andrea; Deflorian, Francesca; Deganutti, Giuseppe et al.
Biomolecular Simulations in Structure‐Based Drug Discovery. ed. / Francesco L. Gervasio; Vojtech Spiwok. Wiley, 2018. p. 225-246 (Methods and Principles in Medicinal Chemistry).

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

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abstract = "G protein–coupled receptors (GPCRs) represent a superfamily of receptors linked to a wide range of human diseases. The increasing number of X-ray diffraction crystal structures now available provides a solid foundation to understand the nature of key protein–ligand interactions at the final stage of the mutual recognition process. They enable structure-based drug design (SBDD), and are an important starting point for computer-aided biophysical investigations, including molecular dynamics (MD) simulations. Recently, MD-based approaches have been successfully applied to understand ligand–GPCR binding at a molecular level. Promising approaches and case studies of MD methods applied to SBDD include (i) analysis of locations and thermodynamic properties of water molecules; (ii) ligand-binding free energy predictions; (iii) ligand-binding event and kinetics evaluations.",

keywords = "ABMD, GPCR ligand design, ligand-receptor binding, molecular dynamics simulations, protein-ligand binding free energy, SBDD, water molecule-mediated interactions",

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T1 - Molecular Dynamics Applications to GPCR Ligand Design

AU - Bortolato, Andrea

AU - Deflorian, Francesca

AU - Deganutti, Giuseppe

AU - Sabbadin, Davide

AU - Moro, Stefano

AU - Mason, Jonathan S.

PY - 2018/12/10

Y1 - 2018/12/10

N2 - G protein–coupled receptors (GPCRs) represent a superfamily of receptors linked to a wide range of human diseases. The increasing number of X-ray diffraction crystal structures now available provides a solid foundation to understand the nature of key protein–ligand interactions at the final stage of the mutual recognition process. They enable structure-based drug design (SBDD), and are an important starting point for computer-aided biophysical investigations, including molecular dynamics (MD) simulations. Recently, MD-based approaches have been successfully applied to understand ligand–GPCR binding at a molecular level. Promising approaches and case studies of MD methods applied to SBDD include (i) analysis of locations and thermodynamic properties of water molecules; (ii) ligand-binding free energy predictions; (iii) ligand-binding event and kinetics evaluations.

AB - G protein–coupled receptors (GPCRs) represent a superfamily of receptors linked to a wide range of human diseases. The increasing number of X-ray diffraction crystal structures now available provides a solid foundation to understand the nature of key protein–ligand interactions at the final stage of the mutual recognition process. They enable structure-based drug design (SBDD), and are an important starting point for computer-aided biophysical investigations, including molecular dynamics (MD) simulations. Recently, MD-based approaches have been successfully applied to understand ligand–GPCR binding at a molecular level. Promising approaches and case studies of MD methods applied to SBDD include (i) analysis of locations and thermodynamic properties of water molecules; (ii) ligand-binding free energy predictions; (iii) ligand-binding event and kinetics evaluations.

KW - ABMD

KW - GPCR ligand design

KW - ligand-receptor binding

KW - molecular dynamics simulations

KW - protein-ligand binding free energy

KW - SBDD

KW - water molecule-mediated interactions

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U2 - 10.1002/9783527806836.ch9

DO - 10.1002/9783527806836.ch9

M3 - Chapter

SN - 9783527342655

T3 - Methods and Principles in Medicinal Chemistry

SP - 225

EP - 246

BT - Biomolecular Simulations in Structure‐Based Drug Discovery

A2 - Gervasio, Francesco L.

A2 - Spiwok, Vojtech

PB - Wiley

ER -

Molecular Dynamics Applications to GPCR Ligand Design

Abstract

Publication series

Bibliographical note

Keywords

UN SDGs

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