Force Field Development for Protein Absorption Modeling

蛋白质吸收建模的力场开发

基本信息

批准号：
7599006
负责人：
ROBERT A LATOUR
金额：
$ 34.55万
依托单位：
CLEMSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-06-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7599006
关键词：
Address Adsorption Agreement Amber Area Behavior Benchmarking Binding Binding Sites Biochemistry Biocompatible Materials Biophysics Biotin Chemistry Circular Dichroism Code Collaborations Communities Complex Controlled Study Data Data Set Development Developmental Process Equilibrium Evaluation Fibronectins Foundations Free Energy Gambling Generations Goals Gold Hybrids Implant Individual Institutes Integrin Binding Integrins Interdisciplinary Study Label Letters Liquid substance Mathematics Measures Medical Device Medical Device Designs Membrane Proteins Methods Modeling Modification Molecular Molecular Conformation Molecular Models Monoclonal Antibodies National Heart, Lung, and Blood Institute Patient Care Peptides Performance Phase Polymers Potential Energy Probability Process Property Protein Fragment Proteins Regenerative Medicine Research Research Personnel Research Subjects Role Saline Sampling Science Secondary Protein Structure Series Simulate Solid Solutions Source Code Spectrometry, Mass, Secondary Ion Spectrum Analysis Surface Surface Plasmon Resonance System Techniques Technology Testing Time Tissue Engineering United States National Institutes of Health Validation Water Work absorption aqueous base biomaterial compatibility clinically relevant computer science design direct application experience functional group improved interest interfacial molecular modeling monolayer prevent programs research study response simulation solid solution tool web site

项目摘要

DESCRIPTION (provided by applicant): Because of its governing role in implant biocompatibility, the understanding and control of protein adsorption to implant surfaces continues to be one of the major areas of research in the field of biomaterials. Although greatly desired, a detailed molecular-level understanding of how protein adsorption occurs, and how to control it, are still lacking. Molecular simulation offers great potential to help address these limitations by providing a tool to accurately predict and visualize molecular-level behavior. However, before this potential can be realized, methods must be specifically developed for this application. The overall objective of the proposed R01 research program is therefore to develop molecular simulation capabilities to accurately simulate protein adsorption on surfaces, initially with polymer-like functionality . This will be accomplished by first modifying the well-established CHARMM molecular simulation program to enable two different force fields (either Class I or II type) to be used in the same simulation to separately represent the solution phase and the solid phase. This will enable both phases of an adsorption system to be accurately modeled by a force field that has been specifically developed and validated for that particular material system (e.g., protein in aqueous solution vs. a crystalline polymer). The interface between the two phases, however, must be separately tuned and validated. To accomplish this, experimental adsorption studies using surface plasmon resonance spectroscopy will be conducted using a designed host-guest peptide system to generate experimental adsorption data that will be used to evaluate, tune, and validate a CHARMM interfacial force field for the accurate simulation of protein adsorption behavior at the solid-solution interface. Once validated, the hybrid force field system will be applied to simulate the adsorption behavior for a biomedically relevant protein on functionalized surfaces and the results will be quantitatively compared with a matched set of experimental studies to demonstrate the developed capabilities to accurately simulate protein adsorption behavior. The successful development of these simulation capabilities will provide the foundations for the establishment of molecular simulation as a valuable tool for the biomaterials community for surface design to study and control protein adsorption behavior at the molecular level, with direct applications for medical device design to enhance implant biocompatibility for improved patient care.

描述（由申请人提供）：由于其在植入物生物相容性中的作用，对蛋白质吸附到植入物表面的理解和控制仍然是生物材料领域的主要研究领域之一。尽管非常满意，但仍然缺乏对蛋白质吸附以及如何控制蛋白质吸附的详细理解。分子模拟通过提供一种工具来准确预测和可视化分子级别的行为，为解决这些局限性提供了巨大的潜力。但是，在实现这一潜力之前，必须专门为本应用程序开发方法。因此，提出的R01研究计划的总体目标是开发分子模拟能力，以准确模拟表面上的蛋白质吸附，最初具有聚合物样功能。这将是通过首先修改良好的CHARMM分子模拟程序来实现的，以使两个不同的力场（I类或II类型）在同一模拟中使用以单独表示溶液相和固相。这将使吸附系统的两个阶段都可以通过已针对该特定材料系统（例如，水溶液中的蛋白质与结晶聚合物）进行了特异性开发和验证的力场准确建模。但是，必须分别对两个阶段之间的接口进行调整和验证。为了实现这一目标，将使用设计的宿主 - 基因肽系统进行使用表面等离子体共振光谱的实验吸附研究，以生成实验吸附数据，该数据将用于评估，调整和验证CHARMM界面界面力场，以精确地在固体分析界面上对蛋白质吸附行为进行准确的模拟。一旦得到验证，将应用杂交力场系统来模拟在功能化表面上生物医学相关蛋白的吸附行为，并且将与匹配的一组实验研究进行定量比较，以证明已开发的功能以准确模拟蛋白质吸附行为。这些仿真能力的成功开发将为建立分子模拟的基础，作为生物材料社区的表面设计社区的有价值工具，以在分子水平研究和控制蛋白质的吸附行为，并直接应用医疗设备设计，以增强植入物生物相容性，以改善改善患者护理。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Assessing the influence of adsorbed-state conformation on the bioactivity of adsorbed enzyme layers.

DOI：
10.1021/la900799m
发表时间：
2009-12-15
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
0
作者：
Fears KP;Latour RA
通讯作者：
Latour RA

Probing the conformation and orientation of adsorbed enzymes using side-chain modification.

DOI：
10.1021/la901885d
发表时间：
2009-08-18
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
0
作者：
Fears KP;Sivaraman B;Powell GL;Wu Y;Latour RA
通讯作者：
Latour RA

Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury.

DOI：
10.1016/j.phymed.2010.01.009
发表时间：
2010-08
期刊：
PHYTOMEDICINE
影响因子：
7.9
作者：
Swaminathan, J. K.;Khan, M.;Mohan, I. K.;Selvendiran, K.;Devaraj, S. Niranjali;Rivera, B. K.;Kuppusamy, P.
通讯作者：
Kuppusamy, P.

TOF-SIMS 3D imaging of native and non-native species within HeLa cells.

DOI：
10.1021/ac402288d
发表时间：
2013-11-19
期刊：
ANALYTICAL CHEMISTRY
影响因子：
7.4
作者：
Brison, Jeremy;Robinson, Michael A.;Benoit, Danielle S. W.;Muramoto, Shin;Stayton, Patrick S.;Castner, David G.
通讯作者：
Castner, David G.

Benchmark experimental data set and assessment of adsorption free energy for peptide-surface interactions.