III: Small: Facilitating Search in the High-Dimensional Space of Molecular Interactions

III：小：促进分子相互作用高维空间的搜索

• 批准号: 1716195
• 负责人: Bruna Jacobson
• 金额: $ 50.8万
• 依托单位: University of New Mexico
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1716195&HistoricalAwards=false
• 关键词: III; Small; Facilitating; Search; Dimensional

The binding of proteins (receptors) to small molecules (ligands) is often the underlying mechanism behind biological processes such as immune response and cell signaling. Understanding how receptors and ligands bind is fundamental to explaining these biological phenomena, and for innovative drug discovery and design. The exploration will include designing methods for analyzing binding pathways and kinetics, focusing on the extraction of computational features from multiple user runs. The product of this will be used in outreach activities performed by the PIs in K-12 schools and local museums. In addition to being potentially applicable in cutting-edge computational biophysics research, the resources will also provide the ideal interface to teach the public about molecular interactions and the role they play in biological processes such as allergic reactions.This award will develop methods for simulating binding of biomolecules via an interactive collaborative interface that harnesses and integrates multi-user exploration of the energetic landscape through haptic interfaces. This will address the current limitations of molecular docking simulations by facilitating search in the high-dimensional energetic landscape of molecular docking. Results will include a crowd-sourced high-dimensional dataset of energies and molecular configuration from which to extract biophysical properties of binding events. The long-term objective of the work is to develop a fast, accurate system to aid drug discovery by identifying docking pathways and ligand-receptor conformations using crowd-sourced information.

蛋白质（受体）与小分子（配体）的结合通常是免疫反应和细胞信号传导等生物过程背后的潜在机制。了解受体和配体如何结合是解释这些生物学现象的基础，也是创新药物发现和设计的基础。探索将包括设计用于分析结合途径和动力学的方法，重点是从多个用户运行中提取计算特征。这一成果将用于初级教育机构在K-12学校和当地博物馆开展的外联活动。除了在尖端计算生物物理学研究中具有潜在的应用价值外，这些资源还将提供理想的界面，向公众讲授分子相互作用及其在过敏反应等生物过程中所起的作用。该奖项将开发通过交互式协作界面模拟生物分子结合的方法，用户通过触觉界面探索充满活力的景观。这将解决目前的限制，分子对接模拟，促进搜索在高维充满活力的景观分子对接。 结果将包括一个众包的能量和分子构型的高维数据集，从中提取结合事件的生物物理特性。这项工作的长期目标是开发一个快速，准确的系统，通过使用众包信息识别对接途径和配体-受体构象来帮助药物发现。

项目成果

A Mobile Game for Crowdsourced Molecular Docking Pathways

众包分子对接途径的手机游戏

• DOI: 10.1145/3359566.3360055
• 发表时间: 2019
• 期刊: Interaction and Games
• 作者: Chavez, Anna;Adamson, Torin;Tapia, Lydia;Jacobson, Bruna
• 通讯作者: Jacobson, Bruna

Player Exploration Patterns in Interactive Molecular Docking with Electrostatic Visual Cues

具有静电视觉提示的交互式分子对接中的玩家探索模式

• DOI: 10.1145/3623264.3624463
• 发表时间: 2023
• 期刊: ACM
• 作者: Liu, Lin;Adamson, Torin;Tapia, Lydia;Jacobson, Bruna
• 通讯作者: Jacobson, Bruna