Computational Studies of the Molecular Basis of Natural and Acquired Resistance to Extremes in Microbes

微生物自然和后天极端抵抗力的分子基础的计算研究

基本信息

批准号：
10348160
负责人：
JENNIFER A SWIFT
金额：
$ 34.53万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-01 至 2023-08-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY Our long-term goal is to understand how microbes are able to withstand remarkable extremes of temperature, pressure, and chemical composition (P-T-X), by determining how the macromolecular structures comprising the microbes are preserved. Our focus is on the effects of high pressure, which are much less understood than those of temperature. Since high-pressure methods are increasingly being used for food preservation, understanding the effects of pressure is important for human health and welfare. Disturbingly, some mesophilic microbes appear to able to withstand ~10 kbar pressures, while piezophilic (pressure-loving) microbes have been found at maximum pressures of ~1.1 kbar. Determining what pressures will disrupt structures of proteins in cell-like conditions will help to define the limiting pressures that microbes can grow at. Our goal for the proposed work is to understand the interplay of P-T effects on proteins by examining enzymes from psychrophiles (cold-loving) and thermophiles (hot-loving) that are also piezophilic at different P-T. Based on our previous work on a piezophilic psychrophile enzyme, microbes may be mainly adapted for temperature rather than high pressure and enzymes from psychrophiles appear much more fragile than those from thermophiles. The proposed studies will expand the range of growth temperatures of the source organisms to piezophilic thermophile enzymes. They will also address the effects of piezolytes, which are osmolytes that protect against pressure effects, on proteins. Our approach uses molecular dynamics computer simulations and biophysical experiments. Our specific aims are to: Aim 1. Understand piezophilicity in other psychrophile enzymes. Aim 2. Understand piezophilicity in thermophile enzymes. Aim 3. Understand how piezolytes change pressure effects on proteins.

项目摘要我们的长期目标是了解微生物如何能够承受极大的极端温度，压力和化学成分（P-T-X），通过确定大分子如何保留包含微生物的结构。我们的重点是高压的影响，比温度少得多。由于越来越多地使用高压方法为了保存食物，了解压力的影响对人类健康和福利很重要。令人不安的是，某些嗜嗜微生物似乎能够承受约10 kbar的压力，而压” （热爱压力）微生物的最大压力约为1.1 kbar。确定什么压力将破坏在细胞状条件下蛋白质的结构，将有助于定义限制压力微生物可以生长。我们提出的工作的目标是了解P-T对蛋白质影响的相互作用从精神噬菌体（热爱）和热疗（热爱）中检查酶，它们也是压抑的在不同的p-t。根据我们以前关于压降精神噬菌体酶的工作，微生物可能主要是适用于温度而不是高压，而来自精神噬菌体的酶显得更多比来自嗜热的脆弱。拟议的研究将扩大生长温度的范围致命的嗜热酶的源生物。他们还将解决压电者的影响，是防止压力影响的渗透剂，对蛋白质。我们的方法使用分子动力学计算机模拟和生物物理实验。我们的具体目的是：目标1。了解其他精神噬菌酶中的压电性。目标2。了解嗜热酶中的压电性。目标3。了解压电方法如何改变对蛋白质的压力影响。