ALX/FPR2 Activation by Stereoisomers of D1 Resolvins Elucidating with Molecular Dynamics Simulation

被引:2
作者
Nunes, Vinicius S. [1 ,2 ]
Abrahao, Odonirio, Jr. [2 ]
Rogerio, Alexandre P. [3 ]
Serhan, Charles N. [4 ,5 ]
机构
[1] Petropolis, Lab Nacl Computacao Cient, BR-25651076 Rio De Janeiro, Brazil
[2] Univ Fed Triangulo Mineiro, Lab Quim Computac Med, BR-38025180 Uberaba, MG, Brazil
[3] Univ Fed Triangulo Mineiro, Lab Imunofarmacol Expt, BR-38025180 Uberaba, MG, Brazil
[4] Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA
[5] Harvard Med Sch, Boston, MA 02115 USA
关键词
GENERAL FORCE-FIELD; LIPID MEDIATORS; LIPOXIN A(4); SOFTWARE NEWS; INFLAMMATION; RESOLUTION; CHARMM; IDENTIFICATION; MECHANISMS; RECEPTORS;
D O I
10.1021/acs.jpcb.3c01787
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Chronic inflammation contributes to several diseases,but its resolutionis driven by specialized pro-resolving mediators (SPM) such as resolvinD1 (RvD1) and its epimer aspirin-triggered resolvin D1 (AT-RvD1),both biosynthesized from & omega;-3 fatty docosahexaenoic acid (DHA).RvD1 and AT-RvD1 have anti-inflammatory and pro-resolution potentials,and their effects could be mediated by formyl peptide receptor type2 receptor ALX/FPR2, a G-protein-coupled receptor (GPCR). In thiswork, we performed 44 & mu;s of molecular dynamics simulations withtwo complexes: FPR2@AT-RvD1 and FPR2@RvD1. Our results show the following:(i) in the AT-RvD1 simulations, the ALX/FPR2 receptor remained inthe active state in 62% of the frames, while in the RVD1 simulations,the receptor remained in the active state in 74% of the frames; (ii)two residues, R201 and R205, of ALX/FPR2 appear, establishing interactionswith both resolvins in all simulations (22 in total); (iii) RvD1 hydrogenbonds with R201 and R205 presented higher frequency than AT-RvD1;and (iv) residues R201 and R205 are the two receptor hotspots, demonstratedby the binding free calculations. Such results show that the ALX/FPR2receptor remained in the active state for longer in the FPR2@RvD1simulations than in the FPR2@AT-RvD1 simulations.
引用
收藏
页码:6479 / 6486
页数:8
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