CAREER: Unraveling Molecular Mechanisms of Biomineralization

职业：揭示生物矿化的分子机制

• 批准号: 0955071
• 负责人: Hendrik Heinz
• 金额: $ 43万
• 依托单位: University of Akron
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0955071&HistoricalAwards=false
• 关键词: CAREER; Unraveling; Molecular; Mechanisms; Biomineralization

TECHNICAL SUMMARYThis CAREER award supports computational research and education to advance the fundamental understanding of biomineralization processes, with an emphasis on silica and hydroxyapatite assembly in the presence of short proteins in aqueous solution. This includes quantum-mechanical calculations, the development of state-of-the-art force fields, coarse-grain models, and understanding experimental observations at the molecular scale to unravel interactions which enable and control the formation and properties of biominerals, bone, and teeth. Knowledge of these molecular-scale interactions will guide in the synthesis of specific biological templates such as peptides and small proteins to assemble precursors into minerals of desired shape and properties. Potential applications include new separation media and catalyst supports, artificial bone and dental materials, and molecular therapeutics for removal of mineral deposits in atherosclerosis.This research will address current difficulties in understanding the specific binding of biomolecules to inorganic surfaces. Accurate molecular models will be made available to investigate such interfaces at length scales of 10 nanometers and time scales exceeding 10 nanoseconds in full atomic resolution. Specifically, methodology development includes: (1) force fields for silica Q2, Q3, and Q4 surfaces and various ratios between silanol and siloxide groups which quantitatively reproduce surface and interface tensions measured in experiment, (2) similarly accurate force fields for hydroxyapatite and fluoroapatite, (3) equilibration algorithms and analysis tools for the simulation of non-covalent self-assembly of nanostructures of different morphology, (4) the development of multiscale simulation approaches from ab-initio to coarse-grain models and bioinformatics approaches. Force field development will rely on previously developed methods which enable one order of magnitude more accurate computations of interfacial thermodynamic properties compared to earlier models. Results of molecular dynamics, Monte Carlo, and bioinformatics methods will be related to experimental data by collaborators to understand concentration- and chemistry-dependent changes in self-assembly and growth of nanostructures. An important goal of this research is to advance the theory of biological self-assembly and biomineralization with an aim toward synthesis and characterization of novel biomaterials through collaborations with experimentalists.The educational activities of this CAREER award include training graduate and undergraduate students, as well as new course development in computational materials science. Related STEM concepts will also be introduced to High School students through hands-on projects at the University of Akron in the labs of several researchers as part of the Advanced Placement chemistry program. An Annual Engineering Career Day will be organized at the University of Akron, including presentations and interactive sessions across several engineering disciplines to introduce High School students to intellectual challenges and career opportunities in engineering. High School teachers will be engaged in these activities in collaboration with the University of Akron. The PI will also organize the first two rounds of the US National Chemistry Olympiad for High School students every year which covers participation from 72 High Schools in a three-County region around Akron, Ohio.NON-TECHNICAL SUMMARYThis CAREER award supports computational research and education to advance the fundamental understanding of the creation of biological mineral structures such as diatoms, seashells, bone, and teeth. This is a common process in nature for the synthesis of structural and highly functional materials under environmentally friendly conditions. The PI will use theoretical models and computation to gain insight into the formation of complex biominerals, bone, and teeth and to guide the synthesis of materials that mimic those created by living organisms. Potential applications include materials for orthopedics, and molecular therapeutics for atherosclerosis. The educational activities of this CAREER award include training graduate and undergraduate students, as well as new course development in computational materials science. Related STEM concepts will also be introduced to High School students through hands-on projects at the University of Akron in the labs of several researchers as part of the Advanced Placement chemistry program. An Annual Engineering Career Day will be organized at the University of Akron, including presentations and interactive sessions across several engineering disciplines to introduce High School students to intellectual challenges and career opportunities in engineering. High School teachers will be engaged in these activities in collaboration with the University of Akron. The PI will also organize the first two rounds of the US National Chemistry Olympiad for High School students every year which covers participation from 72 High Schools in a three-County region around Akron, Ohio.

技术摘要这一职业奖支持计算研究和教育，以提高对生物矿化过程的基本理解，并重点是在水溶液中存在短蛋白的情况下，重点是二氧化硅和羟基磷灰石组装。这包括量子力学计算，最先进的力场的发展，粗晶粒模型以及在分子尺度上理解实验观测，以解开相互作用，从而启用和控制生物矿物质，骨骼和牙齿的形成和特性。这些分子尺度相互作用的知识将指导特定的生物模板（例如肽和小蛋白质），以将前体组装成所需形状和特性的矿物质。潜在的应用包括新的分离培养基和催化剂支持，人造骨和牙科材料，以及分子疗法以去除动脉粥样硬化中的矿物沉积物。这项研究将解决当前在理解生物分子与无机表面的特定结合方面的困难。将提供准确的分子模型，以10纳米的长度尺度研究此类界面，并在完全原子分辨率中超过10纳秒的时间尺度。具体而言，方法论的发展包括：（1）二氧化硅Q2，Q3和Q4表面的力场以及在实验中测量的表面和界面张力在实验中测量的硅烷酚和硅氧基组之间的各种比率，（2）类似准确的力场，用于用于远程和液位的静态工具和分析工具的工具，（3）不同形态学的纳米结构，（4）从Ab-Initio到粗粒模型和生物信息学方法的多尺度模拟方法的发展。力场发展将依赖于先前开发的方法，该方法与早期模型相比，一个数量级的界面热力学特性更准确。分子动力学，蒙特卡洛和生物信息学方法的结果将与合作者的实验数据有关，以了解自组装和纳米结构生长的浓度和化学依赖性变化。这项研究的一个重要目的是推进生物学自我组装和生物矿化理论，目的是通过与实验者的合作来综合和表征新型生物材料。该职业奖的教育活动包括培训研究生和本科生，以及计算材料科学领域的新课程开发。相关的STEM概念还将通过阿克伦大学的几位研究人员的实验室的动手项目介绍给高中生，这是高级安置化学计划的一部分。年度工程职业日将在阿克伦大学组织，包括几个工程学科的演讲和互动会议，以向高中生介绍工程学的智力挑战和职业机会。高中老师将与阿克伦大学合作从事这些活动。 The PI will also organize the first two rounds of the US National Chemistry Olympiad for High School students every year which covers participation from 72 High Schools in a three-County region around Akron, Ohio.NON-TECHNICAL SUMMARYThis CAREER award supports computational research and education to advance the fundamental understanding of the creation of biological mineral structures such as diatoms, seashells, bone, and teeth.这是在环保条件下合成结构和高度功能材料的共同过程。 PI将使用理论模型和计算来深入了解复杂的生物矿物质，骨骼和牙齿的形成，并指导模仿生物体产生的材料的综合。潜在的应用包括骨科材料和动脉粥样硬化的分子疗法。该职业奖的教育活动包括培训研究生和本科生，以及计算材料科学的新课程开发。相关的STEM概念还将通过阿克伦大学的几位研究人员的实验室的动手项目介绍给高中生，这是高级安置化学计划的一部分。年度工程职业日将在阿克伦大学组织，包括几个工程学科的演讲和互动会议，以向高中生介绍工程学的智力挑战和职业机会。高中老师将与阿克伦大学合作从事这些活动。 PI还将每年为高中学生组织美国国家化学奥林匹克运动的前两轮比赛，涵盖俄亥俄州阿克伦附近三县地区72个高中的参与。