A COMBINED COMPUTATIONAL AND EXPERIMENTAL STUDY ON THE LIGAND-GATING IN CNG AND

CNG 和配体门控的综合计算和实验研究

• 批准号: 7723187
• 负责人: Lei Zhou
• 金额: $ 0.05万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723187
• 关键词: Address; Computer Retrieval of Information on Scientific Projects Database; Data; Electrostatics; Funding; Grant; Institution; Ligands; Proteins; Published Comment; Research; Research Personnel; Resources; Solvents; Source; United States National Institutes of Health; improved; research study; response; size

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We appreciate the comments on the renewal application for MRAC MCB060027, A combined computational and experimental study on the ligand - gating in CNG and HCN channels, by Lei Zhou and Steven A. Siegelbaum. We found that most of the comments from both anonymous reviewers were very constructive and helpful for us to further improve the original proposal. As quoted in the Proposal Comments by Allocation Staff, one of the major technical concerns by reviewer 1 is on the weakness in the application of TI. Actually we had carried out the TI almost exactly as described by reviewer 1 (first removing electrostatic and then VDW interactions; comparing the difference between removing ligand from protein and versus removing it from bulk solvent). However, we were concerned with the file size (already 15 pages) so that we didnt present all the technical details or preliminary results in the renewal application. Here we carefully address concerns raised by both reviewers and add those technical details together with the related preliminary data. We hope that this response together with the original renewal application will satisfy these concerns and enable this proposal to be found acceptable so that we may continue the research proposed in this MRAC renewal application. Thank you for your consideration.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们感谢对MRAC MCB 060027的更新申请的评论，一个关于CNG和HCN通道中配体门控的计算和实验研究，由Lei Zhou和Steven A.西格尔鲍姆我们发现，这两位匿名评论者的大多数意见都非常有建设性，有助于我们进一步改进最初的提案。正如编配人员的建议意见所引述，检讨人员1的其中一项主要技术关注，是技术指标在应用方面的弱点。实际上，我们几乎完全按照评审员1的描述进行了TI（首先去除静电，然后VDW相互作用;比较从蛋白质中去除配体与从本体溶剂中去除配体之间的差异）。然而，我们关心的文件大小（已经15页），使我们没有提出所有的技术细节或初步结果，在续期申请。在这里，我们仔细解决了两位评审员提出的问题，并将这些技术细节与相关的初步数据一起添加进去。我们希望本回复连同原始更新申请将满足这些担忧，并使该提案被认为是可接受的，以便我们可以继续进行本MRAC更新申请中提出的研究。谢谢你的考虑。