Structural causes, control mechanisms and consequences of small-molecule protein binding promiscuity

小分子蛋白结合混乱的结构原因、控制机制和后果

基本信息

  • 批准号:
    371872-2009
  • 负责人:
  • 金额:
    $ 1.31万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2011
  • 资助国家:
    加拿大
  • 起止时间:
    2011-01-01 至 2012-12-31
  • 项目状态:
    已结题

项目摘要

The cellular environment is a crowded, unforgiving environment far from the controlled conditions encountered in test tubes. From a thermodynamic point of view, in these conditions, there should be competition between proteins for small-molecules and vice versa. The extent to which this occurs is influenced by the evolution of protein function, that requires not only the ability to bind specific small molecules but also the mechanisms to keep in check the competition. This phenomenon of small-molecule/protein binding promiscuity has been largely ignored over the years and it is crucial in improving our knowledge of molecular recognition, evolution and cellular function. The proposed research program will develop the tools and resources necessary to study the structural causes and control mechanisms of small-molecule protein binding promiscuity at a systems level. The primary objectives of the proposed research program are: 1. The development of methods for the detection of binding site similarities 2: The development of methods for the simulation of dynamic aspects of protein function, and 3. The mapping of experimental and modelled protein structural information into reconstructed metabolic networks to integrate structural and systems biology and use of the methods developed to understand molecular recognition and exploit it in drug design. The novelty of the research plan lies in the powerful new methods proposed and their use to understanding molecular recognition from a structural systems biology point of view. The proposed research plan will develop and integrate structural computational biology tools as well as bio- and chemo-informatics resources and represents a new paradigm for understanding molecular recognition. The interdisciplinary nature of this program will contribute to the formation of students from diverse backgrounds to work at the interface of chemistry, molecular biology, physics and computer sciences.
细胞环境是一个拥挤的,无情的环境,远离试管中遇到的受控条件。从热力学的角度来看,在这些条件下,蛋白质之间应该存在对小分子的竞争,反之亦然。这种情况发生的程度受到蛋白质功能进化的影响,这不仅需要结合特定小分子的能力,还需要控制竞争的机制。这种小分子/蛋白质结合混杂的现象多年来在很大程度上被忽视了,它对提高我们对分子识别,进化和细胞功能的认识至关重要。拟议的研究计划将开发必要的工具和资源,以研究小分子蛋白质结合混杂在系统水平上的结构原因和控制机制。拟议研究计划的主要目标是:1。开发用于检测结合位点相似性的方法2:开发用于模拟蛋白质功能的动态方面的方法,以及3。将实验和建模的蛋白质结构信息映射到重建的代谢网络中,以整合结构和系统生物学,并使用开发的方法来理解分子识别并将其用于药物设计。该研究计划的新奇在于提出了强大的新方法,并从结构系统生物学的角度来理解分子识别。拟议的研究计划将开发和整合结构计算生物学工具以及生物和化学信息学资源,并代表理解分子识别的新范式。该计划的跨学科性质将有助于形成来自不同背景的学生在化学,分子生物学,物理学和计算机科学的接口工作。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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Najmanovich, Rafael其他文献

The NRGTEN Python package: an extensible toolkit for coarse-grained normal mode analysis of proteins, nucleic acids, small molecules and their complexes
  • DOI:
    10.1093/bioinformatics/btab189
  • 发表时间:
    2021-03-20
  • 期刊:
  • 影响因子:
    5.8
  • 作者:
    Mailhot, Olivier;Najmanovich, Rafael
  • 通讯作者:
    Najmanovich, Rafael
IsoMIF Finder: online detection of binding site molecular interaction field similarities
  • DOI:
    10.1093/bioinformatics/btv616
  • 发表时间:
    2016-02-15
  • 期刊:
  • 影响因子:
    5.8
  • 作者:
    Chartier, Matthieu;Adriansen, Etienne;Najmanovich, Rafael
  • 通讯作者:
    Najmanovich, Rafael
IsoCleft Finder - a web-based tool for the detection and analysis of protein binding-site geometric and chemical similarities.
  • DOI:
    10.12688/f1000research.2-117.v1
  • 发表时间:
    2013-01-01
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kurbatova, Natalja;Chartier, Matthieu;Najmanovich, Rafael
  • 通讯作者:
    Najmanovich, Rafael
Applications of Normal Mode Analysis Methods in Computational Protein Design
  • DOI:
    10.1007/978-1-4939-6637-0_9
  • 发表时间:
    2017-01-01
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Frappier, Vincent;Chartier, Matthieu;Najmanovich, Rafael
  • 通讯作者:
    Najmanovich, Rafael
Analysis of Subpocket Selectivity and Identification of Potent Selective Inhibitors for Matriptase and Matriptase-2
  • DOI:
    10.1021/jm5015633
  • 发表时间:
    2014-12-11
  • 期刊:
  • 影响因子:
    7.3
  • 作者:
    Duchene, Dominic;Colombo, Eloic;Najmanovich, Rafael
  • 通讯作者:
    Najmanovich, Rafael

Najmanovich, Rafael的其他文献

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{{ truncateString('Najmanovich, Rafael', 18)}}的其他基金

Development of an accessible integrated computational protein design software suite
开发易于使用的集成计算蛋白质设计软件套件
  • 批准号:
    RGPIN-2019-05332
  • 财政年份:
    2022
  • 资助金额:
    $ 1.31万
  • 项目类别:
    Discovery Grants Program - Individual
Development of an accessible integrated computational protein design software suite
开发易于使用的集成计算蛋白质设计软件套件
  • 批准号:
    RGPIN-2019-05332
  • 财政年份:
    2021
  • 资助金额:
    $ 1.31万
  • 项目类别:
    Discovery Grants Program - Individual
Development of an accessible integrated computational protein design software suite
开发易于使用的集成计算蛋白质设计软件套件
  • 批准号:
    RGPIN-2019-05332
  • 财政年份:
    2020
  • 资助金额:
    $ 1.31万
  • 项目类别:
    Discovery Grants Program - Individual
Development of an accessible integrated computational protein design software suite
开发易于使用的集成计算蛋白质设计软件套件
  • 批准号:
    RGPIN-2019-05332
  • 财政年份:
    2019
  • 资助金额:
    $ 1.31万
  • 项目类别:
    Discovery Grants Program - Individual
Dynamics in molecular recognition
分子识别动力学
  • 批准号:
    RGPIN-2014-05766
  • 财政年份:
    2018
  • 资助金额:
    $ 1.31万
  • 项目类别:
    Discovery Grants Program - Individual
Dynamics in molecular recognition
分子识别动力学
  • 批准号:
    RGPIN-2014-05766
  • 财政年份:
    2017
  • 资助金额:
    $ 1.31万
  • 项目类别:
    Discovery Grants Program - Individual
A versatile broad range microscale thermophoresis apparatus for the measurement of biomolecular interactions
用于测量生物分子相互作用的多功能大范围微型热泳装置
  • 批准号:
    RTI-2017-00364
  • 财政年份:
    2016
  • 资助金额:
    $ 1.31万
  • 项目类别:
    Research Tools and Instruments
Dynamics in molecular recognition
分子识别动力学
  • 批准号:
    RGPIN-2014-05766
  • 财政年份:
    2016
  • 资助金额:
    $ 1.31万
  • 项目类别:
    Discovery Grants Program - Individual
Dynamics in molecular recognition
分子识别动力学
  • 批准号:
    RGPIN-2014-05766
  • 财政年份:
    2015
  • 资助金额:
    $ 1.31万
  • 项目类别:
    Discovery Grants Program - Individual
Dynamics in molecular recognition
分子识别动力学
  • 批准号:
    RGPIN-2014-05766
  • 财政年份:
    2014
  • 资助金额:
    $ 1.31万
  • 项目类别:
    Discovery Grants Program - Individual

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