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.

项目概要我们的长期目标是了解微生物如何能够承受极端的环境温度、压力和化学成分 (P-T-X)，通过确定大分子如何包含微生物的结构被保留。我们的重点是高压的影响，比对温度的了解要少得多。由于越来越多地使用高压方法对于食品保存，了解压力的影响对于人类健康和福祉非常重要。令人不安的是，一些嗜温微生物似乎能够承受约 10 kbar 的压力，而嗜压微生物在约 1.1 kbar 的最大压力下发现了（喜压）微生物。确定什么压力会破坏类细胞条件下的蛋白质结构将有助于定义极限压力微生物可以生长的地方。我们拟议工作的目标是通过以下方式了解 P-T 效应对蛋白质的相互作用：检查来自嗜冷菌（喜冷）和嗜热菌（喜热）的酶，这些酶也是嗜压的在不同的 P-T 时间。根据我们之前对亲压嗜冷酶的研究，微生物可能主要是适应温度而不是高压，来自嗜冷生物的酶似乎更多比嗜热菌脆弱。拟议的研究将扩大生长温度范围亲压嗜热酶的来源生物。他们还将解决压电电解质的影响，它们是渗透剂，可以防止蛋白质受到压力影响。我们的方法使用分子动力学计算机模拟和生物物理实验。我们的具体目标是：目标 1. 了解其他嗜冷酶的亲压性。目标 2. 了解嗜热酶的亲压性。目标 3. 了解压电电解质如何改变压力对蛋白质的影响。