This title appears in the Scientific Report :
2018
Please use the identifier:
http://dx.doi.org/10.1016/j.bbrc.2018.01.160 in citations.
Please use the identifier: http://hdl.handle.net/2128/19158 in citations.
Predicting ligand binding poses for low-resolution membrane protein models: Perspectives from multiscale simulations
Predicting ligand binding poses for low-resolution membrane protein models: Perspectives from multiscale simulations
Membrane receptors constitute major targets for pharmaceutical intervention. Drug design efforts rely on the identification of ligand binding poses. However, the limited experimental structural information available may make this extremely challenging, especially when only low-resolution homology mo...
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Personal Name(s): | Schneider, Jakob |
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Korshunova, Ksenia / Musiani, Francesco / Alfonso-Prieto, Mercedes (Corresponding author) / Giorgetti, Alejandro / Carloni, Paolo (Corresponding author) | |
Contributing Institute: |
Jara-Institut Quantum Information; INM-11 Computational Biomedicine; INM-9 Computational Biomedicine; IAS-5 |
Published in: | Biochemical and biophysical research communications, 498 (2018) 2, S. 366 - 374 |
Imprint: |
Orlando, Fla.
Academic Press
2018
|
DOI: |
10.1016/j.bbrc.2018.01.160 |
PubMed ID: |
29409902 |
Document Type: |
Journal Article |
Research Program: |
Theory, modelling and simulation Connectivity and Activity |
Link: |
Restricted Published on 2018-02-02. Available in OpenAccess from 2019-02-02. Restricted |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/19158 in citations.
Membrane receptors constitute major targets for pharmaceutical intervention. Drug design efforts rely on the identification of ligand binding poses. However, the limited experimental structural information available may make this extremely challenging, especially when only low-resolution homology models are accessible. In these cases, the predictions may be improved by molecular dynamics simulation approaches. Here we review recent developments of multiscale, hybrid molecular mechanics/coarse-grained (MM/CG) methods applied to membrane proteins. In particular, we focus on our in-house MM/CG approach. It is especially tailored for G-protein coupled receptors, the largest membrane receptor family in humans. We show that our MM/CG approach is able to capture the atomistic details of the receptor/ligand binding interactions, while keeping the computational cost low by representing the protein frame and the membrane environment in a highly simplified manner. We close this review by discussing ongoing improvements and challenges of the current implementation of our MM/CG code |