Computational studies of protegrin antimicrobial peptides: a review.
Computational studies of protegrin antimicrobial peptides: a review.
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DOI：
10.1016/j.peptides.2010.10.006
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发表时间：
2011-01
期刊：
影响因子：
3
通讯作者：
Kaznessis YN
中科院分区：
文献类型：
--
作者：
Bolintineanu DS;Kaznessis YN
抗菌肽（Antimicrobial peptides，AMP）是天然存在的小肽，其表现出强烈的抗菌特性，通常被认为是选择性细菌膜破坏的结果。因此，人们对基于AMP的治疗性抗生素的开发产生了极大的兴趣;然而，对这些肽的基本作用机制的理解不足在很大程度上阻碍了这种努力。我们提出了一个总结的计算和理论研究protegrin，一个特别有效的肽，这是一个很好的模型的作用机制的AMP和一个有前途的治疗候选人。实验研究揭示了保护蛋白作用的许多关键步骤：已知保护蛋白单体在各种脂质环境中二聚化;保护蛋白肽与脂质双层膜，特别是阴离子脂质强烈相互作用;保护蛋白已被证明在脂质双层中形成孔，这导致不受控制的离子转运，可能是细菌死亡的关键因素。在这项工作中，我们提出了一个全面的审查计算和理论研究，补充和扩展的信息从实验工作与protegrins，以及一个简短的调查的实验生物物理研究，是最相关的计算工作。我们表明，一个一致的，机械的描述protegrins的杀菌作用机制正在出现，并简要概述了目前的理解是不足的领域。我们希望，本文回顾的研究提供了令人信服的证据，证明protegrins和其他AMP的计算研究的好处，并为这一领域的未来工作提供了有用的指导。
Antimicrobial peptides (AMPs) are small, naturally-occurring peptides that exhibit strong antibacterial properties generally believed to be a result of selective bacterial membrane disruption. As a result, there has been significant interest in the development of therapeutic antibiotics based on AMPs; however, the poor understanding of the fundamental mechanism of action of these peptides has largely hampered such efforts. We present a summary of computational and theoretical investigations of protegrin, a particularly potent peptide that is both an excellent model for the mechanism of action of AMPs and a promising therapeutic candidate. Experimental investigations have shed light on many of the key steps in the action of protegrin: protegrin monomers are known to dimerize in various lipid environments; protegrin peptides interact strongly with lipid bilayer membranes, particularly anionic lipids; protegrins have been shown to form pores in lipid bilayers, which results in uncontrolled ion transport and may be a key factor in bacterial death. In this work, we present a comprehensive review of the computational and theoretical studies that have complemented and extended the information obtained from experimental work with protegrins, as well as a brief survey of the experimental biophysical studies that are most pertinent to such computational work. We show that a consistent, mechanistic description of the bactericidal mechanism of action of protegrins is emerging, and briefly outline areas where the current understanding is deficient. We hope that the research reviewed herein offers compelling evidence of the benefits of computational investigations of protegrins and other AMPs, as well as providing a useful guide to future work in this area.
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影响因子：
2.1
作者：
Bolintineanu, D. S.;Langham, A. A.;Kaznessis, Y. N.
通讯作者：
Kaznessis, Y. N.
DOI：
10.1085/jgp.27.1.37
发表时间：
1943-09-20
期刊：
The Journal of general physiology
影响因子：
--
作者：
Goldman DE
通讯作者：
Goldman DE
影响因子：
3.4
作者：
Cárdenas, AE;Coalson, RD;Kurnikova, MG
通讯作者：
Kurnikova, MG
DOI：
10.1111/j.1432-1033.1996.0575p.x
发表时间：
1996-05-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Aumelas, A;Mangoni, M;Chavanieu, A
通讯作者：
Chavanieu, A
影响因子：
3.5
作者：
BESSALLE, R;KAPITKOVSKY, A;FRIDKIN, M
通讯作者：
FRIDKIN, M