Insights of structure-based pharmacophore studies and inhibitor design against Gal3 receptor through molecular dynamics simulations

被引:5
作者
Seshan, Gunalan [1 ]
Kanagasabai, Somarathinam [1 ]
Ananthasri, Sailapathi [1 ]
Kannappan, Balaji [2 ]
Suvitha, A. [3 ]
Jaimohan, S. M. [4 ]
Kanagaraj, Sekar [5 ]
Kothandan, Gugan [1 ]
机构
[1] Univ Madras, Ctr Adv Study Crystallog & Biophys, Biopolymer Modelling Lab, Guindy Campus, Chennai 600025, Tamil Nadu, India
[2] Chosun Univ, Dept Life Sci, Natl Res Ctr Dementia, Gwangju, South Korea
[3] CMR Inst Technol, Dept Phys, Bangalore, Karnataka, India
[4] CSIR Cent Leather Res Inst, Adv Mat Lab, Chennai, Tamil Nadu, India
[5] Indian Inst Sci, Dept Computat & Data Sci, Lab Struct Biol & Biocomp, Bangalore, Karnataka, India
关键词
Pharmacophore modeling; GPCRs; homology modeling; Gal3-galanin receptor 3; SNAP 37889 and SNAP 398299; GALANIN; METHODOLOGY; MODELS; POTENT;
D O I
10.1080/07391102.2020.1804452
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Our present work studies the structure-based pharmacophore modeling and designing inhibitor against Gal3 receptor through molecular dynamics (MD) simulations extensively. Pharmacophore models play a key role in computer-aided drug discovery like in the case of virtual screening of chemical databases,de novodrug design and lead optimization. Structure-based methods for developing pharmacophore models are important, and there have been a number of studies combining such methods with the use of MD simulations to model protein's flexibility. The two potential antagonists SNAP 37889 and SNAP 398299 were docked and simulated for 250 ns and the results are analyzed and carried for the structure-based pharmacophore studies. This helped in identification of the subtype selectivity of the binding sites of the Gal3 receptor. Our work mainly focuses on identifying these binding site residues and to design more potent inhibitors compared to the previously available inhibitors through pharmacophore models. The study provides crucial insight into the binding site residues Ala2, Asp3, Ala4, Gln5, Phe24, Gln79, Ala80, Ile82, Tyr83, Trp88, His99, Ile102, Tyr103, Met106, Tyr157, Tyr161, Pro174, Trp176, Arg181, Ala183, Leu184, Asp185, Thr188, Trp248, His251, His252, Ile255, Leu256, Phe258, Trp259, Tyr270, Arg273, Leu274 and His277, which plays a significant role in the conformational changes of the receptor and helps to understand the inhibition mechanism. Communicated by Ramaswamy H. Sarma
引用
收藏
页码:6987 / 6999
页数:13
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