Modeling Hydrophobic and Hydrophilic Interactions
模拟疏水和亲水相互作用
基本信息
- 批准号:6919290
- 负责人:
- 金额:$ 26.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1991
- 资助国家:美国
- 起止时间:1991-01-01 至 2006-07-31
- 项目状态:已结题
- 来源:
- 关键词:aspartic endopeptidaseschemical bindingchemical modelscomputer simulationconformationcyclosporineselectric fieldenzyme activityhuman immunodeficiency virus 1hydropathyintermolecular interactionmethod developmentmolecular dynamicsmolecular polaritypeptidespeptidylprolyl isomeraseprotein bindingprotein protein interaction
项目摘要
DESCRIPTION (provided by applicant): Computer modeling of complex liquids and biological systems is an important tool in biochemistry. With the increasing power of modern computers, it is becoming possible to design new drugs and new biomimetic materials, and to gain understanding of molecular recognition, and the effects of mutations on protein folding. One of the major aims of this proposal is the invention, extension and application of new methods to accelerate the simulation and sampling of conformational states of biomolecular systems. Monte Carlo and molecular dynamics methods for sampling conformational states of biomolecules are often inherently quasi-ergodic. This means that starting in one stable conformation, not all other conformations can be reached on a practical time scale. We aim to devise methods for sampling conformation space in protein systems and other systems characterized by rough energy landscapes, and to apply these new methods to important problems involving the binding of peptides to enzymes and to conformational transitions of peptides.We aim to develop next generation polarizable force fields in order to deal a major impediment to rational drug design. Predictions of binding energies are dependent on the quality of the force field. Existing force fields do not account for known changes in atomic charges when a peptide undergoes a conformation change. Such effects require a chemically accurate polarizable force field that can correctly account for specific hydrogen bonding energies. During the preceding grant period, we based an assigning fluctuating charges and fluctuating dipoles on designated sites on the molecule. This modet has had remarkable success in predicting properties of water, ion solution, amino acids and dipeptides. We have shown that these methods will be used to study conformational dynamics in the (a) of the b-hairpin C-terminus of protein G; (b) the helix-coil transition of homo and hetero oligopeptides; (C) the binding of cyclosporin A to cyclophilin; and (d) conformational transitions in HIV-1 protease.The proposed research will provide new methods and algorithms as well as next generation force field for use in biological simulations. These methods wilt be used to study the binding of cyclosporin A to cvctoohilin and the conformational transitions in HIV-1
描述(由申请人提供):复杂液体和生物系统的计算机建模是生物化学中的重要工具。随着现代计算机功能的不断增强,设计新药和新的仿生材料,以及了解分子识别和突变对蛋白质折叠的影响正成为可能。该提案的主要目的之一是发明、扩展和应用新方法来加速生物分子系统的构象状态的模拟和采样。蒙特卡罗和分子动力学方法采样的生物分子的构象状态往往是固有的准遍历。这意味着从一种稳定的构象开始,在实际的时间尺度上并不是所有其他构象都能达到。我们的目标是设计方法采样构象空间的蛋白质系统和其他系统的特点是粗糙的能量景观,并将这些新的方法应用到重要的问题,涉及结合的肽酶和肽的构象transformations.We的目标是开发下一代极化力场,以处理一个主要障碍,合理的药物设计。结合能的预测取决于力场的质量。当肽经历构象变化时,现有的力场不能解释原子电荷的已知变化。这种效应需要一个化学上精确的可极化力场,可以正确地解释特定的氢键能。在前一个资助期间,我们基于在分子上指定位置分配波动电荷和波动偶极子。该模型在预测水、离子溶液、氨基酸和二肽等物质的性质方面取得了显著的成功。这些方法可用于研究蛋白质G的b-发夹C-末端、同型和异型寡肽的螺旋-卷曲转变、环孢菌素A与亲环素的结合、环孢菌素A与亲环素的构象动力学、环孢菌素A与亲环素的构象动力学和环孢菌素A与亲环素的构象动力学。和(d)HIV-1中的构象转变1蛋白酶。所提出的研究将提供新的方法和算法以及下一代力场用于生物模拟。这些方法将用于研究环孢素A与cvctoohilin的结合以及HIV-1的构象转变
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 }}
BRUCE J BERNE其他文献
BRUCE J BERNE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('BRUCE J BERNE', 18)}}的其他基金
USING ANTON TO PROBE THE CONFORMATIONAL SPACE OF POLY-GLUTAMINE AND ITS AGGREGA
利用ANTON探测聚谷氨酰胺及其聚集体的构象空间
- 批准号:
8364205 - 财政年份:2011
- 资助金额:
$ 26.84万 - 项目类别:
FLUCTUATING CHARGE MODELS FOR MOLECULAR SIMULATIONS
分子模拟的波动电荷模型
- 批准号:
6314226 - 财政年份:2000
- 资助金额:
$ 26.84万 - 项目类别:
FLUCTUATING CHARGE MODELS FOR MOLECULAR SIMULATIONS
分子模拟的波动电荷模型
- 批准号:
6282736 - 财政年份:1998
- 资助金额:
$ 26.84万 - 项目类别:
FLUCTUATING CHARGE MODELS FOR MOLECULAR SIMULATIONS
分子模拟的波动电荷模型
- 批准号:
6253713 - 财政年份:1997
- 资助金额:
$ 26.84万 - 项目类别:
MODELING HYDROPHOBIC AND HYDROPHILLIC INTERACTIONS
模拟疏水和亲水相互作用
- 批准号:
2459403 - 财政年份:1991
- 资助金额:
$ 26.84万 - 项目类别:
Modeling Hydrophobic and Hydrophilic Interactions
模拟疏水和亲水相互作用
- 批准号:
8393507 - 财政年份:1991
- 资助金额:
$ 26.84万 - 项目类别:
Modeling Hydrophobic and Hydrophilic Interactions
模拟疏水和亲水相互作用
- 批准号:
7681654 - 财政年份:1991
- 资助金额:
$ 26.84万 - 项目类别:
MODELING HYDROPHOBIC AND HYDROPHILIC INTERACTIONS
模拟疏水和亲水相互作用
- 批准号:
6385967 - 财政年份:1991
- 资助金额:
$ 26.84万 - 项目类别:
相似海外基金
Theory of chemical binding in beyond-Born-Oppenheimer chemistry and its applications to complex molecular systems
超生奥本海默化学中的化学结合理论及其在复杂分子系统中的应用
- 批准号:
20H00373 - 财政年份:2020
- 资助金额:
$ 26.84万 - 项目类别:
Grant-in-Aid for Scientific Research (A)