Journal
JOURNAL OF CHEMICAL INFORMATION AND MODELING
Volume 53, Issue 5, Pages 1168-1178Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ci300610w
Keywords
-
Categories
Funding
- University of Nottingham Malaysia Campus
- EPSRC [EP/K039490/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/K039490/1] Funding Source: researchfish
Ask authors/readers for more resources
Molecular dynamics (MD) simulations of membrane-embedded G-protein coupled receptors (GPCRs) have rapidly gained popularity among the molecular simulation community in recent years, a trend which has an obvious link to the tremendous pharmaceutical importance of this group of receptors and the increasing availability of crystal structures. In view of the widespread use of this technique, it is of fundamental importance to ensure the reliability and robustness of the methodologies so they yield valid results and enable sufficiently accurate predictions to be made. In this work, 200 ns simulations of the A2a adenosine receptor (A2a AR) have been produced and evaluated in the light of these requirements. The conformational dynamics of the target protein, as obtained from replicate simulations in both the presence and absence of an inverse agonist ligand (ZM241385), have been investigated and compared using principal component analysis (PCA). Results show that, on this time scale, convergence of the replicates is not readily evident and dependent on the types of the protein motions considered. Thus rates of inter- as opposed to intrahelical relaxation and sampling can be different. When studied individually, we find that helices III and IV have noticeably greater stability than helices I, II, V, VI, and VII in the apo form. The addition of the inverse agonist ligand greatly improves the stability of all helices.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available