CAREER: Unraveling Molecular Mechanisms of Biomineralization

该职业奖支持计算研究和教育，以推进对生物矿化过程的基本理解，重点是在水溶液中存在短蛋白的二氧化硅和羟基磷灰石组装。这包括量子力学计算，最先进力场的发展，粗颗粒模型，以及在分子尺度上理解实验观察，以揭示能够和控制生物矿物，骨骼和牙齿的形成和特性的相互作用。这些分子尺度相互作用的知识将指导特定生物模板的合成，如肽和小蛋白质，将前体组装成所需形状和性质的矿物质。潜在的应用包括新的分离介质和催化剂支撑，人工骨和牙科材料，以及用于去除动脉粥样硬化中矿物质沉积物的分子疗法。这项研究将解决目前在理解生物分子与无机表面的特定结合方面的困难。精确的分子模型将在10纳米的长度尺度和超过10纳秒的时间尺度上以全原子分辨率研究这些界面。具体而言，方法开发包括：(1)二氧化硅Q2、Q3和Q4表面的力场以及硅醇和硅氧化物基团之间的不同比例，可以定量再现实验中测量的表面和界面张力；(2)羟基磷灰石和氟磷灰石的力场同样精确；(3)用于模拟不同形态纳米结构非共价自组装的平衡算法和分析工具。(4)从从头算到粗粒度模型和生物信息学的多尺度模拟方法的发展。力场的发展将依赖于先前开发的方法，与早期的模型相比，这些方法能够更精确地计算界面热力学性质。分子动力学、蒙特卡罗和生物信息学方法的结果将与实验数据相关联，以了解纳米结构自组装和生长中浓度和化学依赖的变化。本研究的一个重要目标是通过与实验工作者的合作，推进生物自组装和生物矿化理论，旨在合成和表征新型生物材料。该奖项的教育活动包括培养研究生和本科生，以及开发计算材料科学的新课程。作为大学先修化学课程的一部分，相关的STEM概念也将通过在阿克伦大学实验室的几位研究人员的动手项目介绍给高中生。阿克伦大学将组织一年一度的工程职业日，包括跨几个工程学科的演讲和互动会议，向高中生介绍工程方面的智力挑战和职业机会。高中教师将与阿克伦大学合作参与这些活动。PI还将每年组织前两轮面向高中生的美国国家化学奥林匹克竞赛，包括俄亥俄州阿克伦周围三个县地区的72所高中的参加。该职业奖支持计算研究和教育，以促进对生物矿物结构（如硅藻、贝壳、骨骼和牙齿）形成的基本理解。这是自然界在环境友好条件下合成结构和高功能材料的常见过程。PI将使用理论模型和计算来深入了解复杂生物矿物质、骨骼和牙齿的形成，并指导模仿生物体产生的材料的合成。潜在的应用包括骨科材料和动脉粥样硬化的分子治疗。该奖项的教育活动包括培养研究生和本科生，以及开发计算材料科学的新课程。作为大学先修化学课程的一部分，相关的STEM概念也将通过在阿克伦大学实验室的几位研究人员的动手项目介绍给高中生。阿克伦大学将组织一年一度的工程职业日，包括跨几个工程学科的演讲和互动会议，向高中生介绍工程方面的智力挑战和职业机会。高中教师将与阿克伦大学合作参与这些活动。PI还将每年组织前两轮面向高中生的美国国家化学奥林匹克竞赛，包括俄亥俄州阿克伦周围三个县地区的72所高中的参加。

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.