Fibroblast growth factor 5 (FGF5) and its missense mutant FGF5-H174 underlying trichomegaly: a molecular dynamics simulation investigation

化学 分子动力学 氢键 错义突变 对接(动物) 蛋白质结构 突变体 结合位点 大分子对接 拉马钱德兰地块 结晶学 立体化学 生物物理学 突变 生物化学 生物 计算化学 基因 医学 护理部 有机化学 分子
作者
Skyler H. Hoang
出处
期刊:Journal of Biomolecular Structure & Dynamics [Taylor & Francis]
卷期号:41 (24): 14786-14796 被引量:2
标识
DOI:10.1080/07391102.2023.2188953
摘要

The missense mutation Y174H of FGF5 (FGF5-H174) had been associated with trichomegaly, characterized by abnormally long and pigmented eyelashes. The amino acid tyrosine (Tyr/Y) at position 174 is conserved across many species, proposedly holding important characteristics for the functions of FGF5. Microsecond molecular dynamics simulations along with protein-protein docking and residue interacting network analysis were employed to investigate the structural dynamics and binding mode of both wild-type (FGF5-WT) and its mutated counterpart (FGF5-H174). It was found that the mutation decreased number of hydrogen bonds within the protein, sheet secondary structure, interaction of residue 174 with other residues, and number of salt-bridges. On the other hand, the mutation increased solvent accessible surface area, number of hydrogen bonds between the protein and solvent, coil secondary structure, protein C-alpha backbone root mean square deviation, protein residue root mean square fluctuations, as well as occupied conformational space. In addition, protein-protein docking integrated with molecular dynamics simulations and molecular mechanics - Poisson-Boltzmann surface area (MM/PBSA) binding energy calculation demonstrated that the mutated variant possessed stronger binding affinity towards fibroblast growth factor receptor 1 (FGFR1). However, residue interaction network analysis demonstrated that the binding mode of the FGFR1-FGF5-H174 complex was drastically different from that of the FGFR1-FGF5-WT complex. In conclusion, the missense mutation conferred more instability within itself and stronger binding affinity towards FGFR1 with distinctively altered binding mode or residue connectivity. These findings might help explain the decreased pharmacological activity of FGF5-H174 towards FGFR1, underlying trichomegaly.Communicated by Ramaswamy H. Sarma.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
Ava应助科研通管家采纳,获得10
刚刚
所所应助科研通管家采纳,获得10
1秒前
大模型应助科研通管家采纳,获得10
1秒前
Jasper应助丁丁采纳,获得10
1秒前
1秒前
852应助LCW采纳,获得10
1秒前
孤独的怜阳完成签到,获得积分20
2秒前
啤酒人完成签到 ,获得积分10
4秒前
5秒前
SYLH应助虚心的静枫采纳,获得20
5秒前
义气聪展完成签到 ,获得积分10
8秒前
ommphey发布了新的文献求助100
9秒前
leranlily完成签到,获得积分10
9秒前
MANGMANG发布了新的文献求助10
10秒前
10秒前
10秒前
10秒前
Jasper应助Yuanyuan采纳,获得10
11秒前
李物发布了新的文献求助20
12秒前
quhayley应助樊珩采纳,获得10
15秒前
zhi发布了新的文献求助10
15秒前
Nikola完成签到 ,获得积分10
15秒前
16秒前
英吉利25发布了新的文献求助10
16秒前
19秒前
20秒前
N型半导体发布了新的文献求助10
21秒前
小二郎应助wwpedd采纳,获得30
21秒前
QIU关闭了QIU文献求助
21秒前
回家睡觉发布了新的文献求助30
22秒前
凶狠的惜海完成签到,获得积分20
22秒前
23秒前
媛桃子完成签到 ,获得积分10
23秒前
英姑应助孟古采纳,获得10
26秒前
LCW发布了新的文献求助10
26秒前
薄荷花完成签到,获得积分10
27秒前
领导范儿应助Ronnie采纳,获得10
27秒前
木头人应助白衣轻叹采纳,获得10
27秒前
共享精神应助lalala采纳,获得10
28秒前
29秒前
高分求助中
The Mother of All Tableaux Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 2400
Ophthalmic Equipment Market by Devices(surgical: vitreorentinal,IOLs,OVDs,contact lens,RGP lens,backflush,diagnostic&monitoring:OCT,actorefractor,keratometer,tonometer,ophthalmoscpe,OVD), End User,Buying Criteria-Global Forecast to2029 2000
Optimal Transport: A Comprehensive Introduction to Modeling, Analysis, Simulation, Applications 800
Official Methods of Analysis of AOAC INTERNATIONAL 600
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 588
T/CIET 1202-2025 可吸收再生氧化纤维素止血材料 500
Comparison of adverse drug reactions of heparin and its derivates in the European Economic Area based on data from EudraVigilance between 2017 and 2021 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3952383
求助须知:如何正确求助?哪些是违规求助? 3497737
关于积分的说明 11088744
捐赠科研通 3228363
什么是DOI,文献DOI怎么找? 1784838
邀请新用户注册赠送积分活动 868913
科研通“疑难数据库(出版商)”最低求助积分说明 801303