Design and application of robust and efficient QM/MM free energy simulation methods for biomolecular systems
生物分子系统稳健高效的 QM/MM 自由能模拟方法的设计与应用
基本信息
- 批准号:10004158
- 负责人:
- 金额:$ 28.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAwardBehaviorBindingBiochemistryBiological ProcessCatalysisChemicalsChemistryComplexCoupledDevelopmentElectrostaticsEnsureEnvironmentEnzymesFree EnergyFreedomGoalsHybridsHydrogen BondingImProvImprove AccessLactamaseLigand BindingLigandsMechanicsMethodologyMethodsMolecularMolecular ConformationMotionNobel PrizePerformancePharmaceutical PreparationsPriceProcessProtocols documentationReactionSamplingSchemeStructureSubstrate InteractionSystemTechniquesThermodynamicsWorkchemical reactioncomputational chemistrycostdesignenzyme substrateflexibilityimprovedinhibitor/antagonistmulti-scale modelingneural networknovelquantumreceptorsimulationtautomertechnique developmenttheoriestool
项目摘要
Project Summary / Abstract
To accurately compute free energies of complex biomolecular systems there are two key prerequisites: the accurate
description of inter- and intramolecular interactions, and adequate sampling of all relevant conformational degrees of
freedom. Include the possibility that conformational dynamics may be coupled to complex electronic processes or
chemical reactions, where quantum mechanical (QM) methods are needed, and this task becomes extremely daunt-
ing. Currently, whenever accurate computations of biomolecular systems are essential, the tool of choice is hybrid
quantum mechanical / molecular mechanical (QM/MM) calculations, however, the application of these techniques to
free energy simulations (FES) is far from common. Herein, we aim to develop a set of robust, efficient, and accurate
new techniques that will make the application of QM/MM FES nearly routine. These methods will be subsequently ap-
plied to study two classes of biomolecular applications that present extreme challenges to current techniques. Namely,
the accurate computation of (1) absolute pKa as a function of ligand binding and reaction (e.g., accounting for tran-
sient interactions), and (2) free energy differences of binding as a function of tautomerism. The scientific results will
be closely tied to activities aimed at improving access to these advanced techniques.
项目摘要/摘要
为了准确地计算复杂生物分子体系的自由能,有两个关键的先决条件:准确的
分子间和分子内相互作用的描述,以及对所有相关构象程度的充分采样
自由。包括构象动力学可能与复杂的电子过程或
需要量子力学(QM)方法的化学反应,这项任务变得极其艰巨-
英。目前,只要生物分子系统的精确计算是必不可少的,选择的工具就是混合工具
然而,量子力学/分子力学(QM/MM)计算,这些技术的应用
自由能模拟(FES)远不常见。在这里,我们的目标是开发一套健壮、有效、准确的fi
将使QM/MM FES的应用近乎常规化的新技术。这些方法随后将被应用于-
致力于研究对当前技术构成极端挑战的两类生物分子应用。也就是说,
(1)作为配体结合和反应的函数的绝对pKa的准确计算(例如,考虑反式
相互作用),以及(2)作为互变异构化函数的结合自由能差。Sciencefic的结果将会是
与旨在改善获得这些先进技术的机会的活动密切相关。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Henry Lee Woodcock III其他文献
Henry Lee Woodcock III的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Henry Lee Woodcock III', 18)}}的其他基金
Design and application of robust and efficient QM/MM free energy simulation methods for biomolecular systems
生物分子系统稳健高效的 QM/MM 自由能模拟方法的设计与应用
- 批准号:
9769790 - 财政年份:2018
- 资助金额:
$ 28.49万 - 项目类别:
Design and application of robust and efficient QM/MM free energy simulation methods for biomolecular systems
生物分子系统稳健高效的 QM/MM 自由能模拟方法的设计与应用
- 批准号:
10260512 - 财政年份:2018
- 资助金额:
$ 28.49万 - 项目类别:
Modern Drug Resistance: Elucidation of Beta-Lactamase Mechanisms of Action
现代耐药性:β-内酰胺酶作用机制的阐明
- 批准号:
7912934 - 财政年份:2009
- 资助金额:
$ 28.49万 - 项目类别:
Modern Drug Resistance: Elucidation of Beta-Lactamase Mechanisms of Action
现代耐药性:β-内酰胺酶作用机制的阐明
- 批准号:
8117168 - 财政年份:2009
- 资助金额:
$ 28.49万 - 项目类别:
Modern Drug Resistance: Elucidation of Beta-Lactamase Mechanisms of Action
现代耐药性:β-内酰胺酶作用机制的阐明
- 批准号:
7386222 - 财政年份:2009
- 资助金额:
$ 28.49万 - 项目类别:
相似海外基金
Doctoral Dissertation Improvement Award: Variability in Silcrete Heat Treatment Technology and Implications for Modern Human Behavior
博士论文改进奖:硅混凝土热处理技术的变异性及其对现代人类行为的影响
- 批准号:
2321951 - 财政年份:2023
- 资助金额:
$ 28.49万 - 项目类别:
Standard Grant
Research Initiation Award: Designing Synthetic Polyglycidol-based Polymeric Networks to Influence Cellular Behavior
研究启动奖:设计基于合成聚缩水甘油的聚合物网络以影响细胞行为
- 批准号:
2200484 - 财政年份:2022
- 资助金额:
$ 28.49万 - 项目类别:
Standard Grant
Research Initiation Award: Establishing the Fundamentals of Spin-Crossover Behavior and Catalysis in Single-Chain Nanoparticle Metallopolymers
研究启动奖:建立单链纳米颗粒金属聚合物中自旋交叉行为和催化的基础
- 批准号:
2200447 - 财政年份:2022
- 资助金额:
$ 28.49万 - 项目类别:
Standard Grant
Research Initiation Award: Investigation on Tribo-charging Behavior of Agricultural Particles in the Development of Water-free Bio-separation Approach for Biomass Residues
研究启动奖:生物质残留物无水生物分离方法开发中农业颗粒摩擦带电行为的研究
- 批准号:
1900894 - 财政年份:2019
- 资助金额:
$ 28.49万 - 项目类别:
Standard Grant
Doctoral Dissertation Improvement Award: The Effect of Population Aggregation on Food Acquisition Behavior
博士论文改进奖:种群聚集对食物获取行为的影响
- 批准号:
1745219 - 财政年份:2017
- 资助金额:
$ 28.49万 - 项目类别:
Standard Grant
Research Initiation Award: Mathematical model of the impact of social behavior in the transmission dynamics of HIV epidemics
研究启动奖:社会行为对艾滋病毒流行传播动态影响的数学模型
- 批准号:
1743812 - 财政年份:2017
- 资助金额:
$ 28.49万 - 项目类别:
Standard Grant
Research Intiation Award: Long Time Behavior for Systems of Coupled Partial Differential Equations
研究启动奖:耦合偏微分方程组的长期行为
- 批准号:
1601127 - 财政年份:2016
- 资助金额:
$ 28.49万 - 项目类别:
Standard Grant
Doctoral Dissertation Improvement Award: Investigating The Effect Of Environmental Variability On Mobility And Territorial Behavior
博士论文改进奖:研究环境变化对流动性和领地行为的影响
- 批准号:
1623771 - 财政年份:2016
- 资助金额:
$ 28.49万 - 项目类别:
Standard Grant
Research Initiation Award: Mathematical model of the impact of social behavior in the transmission dynamics of HIV epidemics
研究启动奖:社会行为对艾滋病毒流行传播动态影响的数学模型
- 批准号:
1505498 - 财政年份:2015
- 资助金额:
$ 28.49万 - 项目类别:
Standard Grant
Doctoral Dissertation Improvement Award: Relationships Between Consumer Behavior And Regional Identity
博士论文改进奖:消费者行为与区域认同的关系
- 批准号:
1550581 - 财政年份:2015
- 资助金额:
$ 28.49万 - 项目类别:
Standard Grant