- 1、本文档共10页,可阅读全部内容。
- 2、原创力文档(book118)网站文档一经付费(服务费),不意味着购买了该文档的版权,仅供个人/单位学习、研究之用,不得用于商业用途,未经授权,严禁复制、发行、汇编、翻译或者网络传播等,侵权必究。
- 3、本站所有内容均由合作方或网友上传,本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺!文档内容仅供研究参考,付费前请自行鉴别。如您付费,意味着您自己接受本站规则且自行承担风险,本站不退款、不进行额外附加服务;查看《如何避免下载的几个坑》。如果您已付费下载过本站文档,您可以点击 这里二次下载。
- 4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等,请点击“版权申诉”(推荐),也可以打举报电话:400-050-0827(电话支持时间:9:00-18:30)。
- 5、该文档为VIP文档,如果想要下载,成为VIP会员后,下载免费。
- 6、成为VIP后,下载本文档将扣除1次下载权益。下载后,不支持退款、换文档。如有疑问请联系我们。
- 7、成为VIP后,您将拥有八大权益,权益包括:VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
- 8、VIP文档为合作方或网友上传,每下载1次, 网站将根据用户上传文档的质量评分、类型等,对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档
查看更多
Novel Allosteric Sites on Ras for Lead Generation 英文参考文献
NovelAllostericSitesonRasforLeadGeneration
BarryJ.Grant1*.,SuryaniLukman3,4*.,HarrisonJ.Hocker5,JaquelineSayyah6,JoanHellerBrown6,
J.AndrewMcCammon2,6,AlemayehuA.Gorfe5*
1Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America, 2Department of Chemistry and
Biochemistry, Center for Theoretical Biological Physics and Howard Hughes Medical Institute, University of California San Diego, La Jolla, California, United States of
America,3BioinformaticsInstitute,AgencyforScience,TechnologyandResearch,Singapore,4DepartmentofChemistry,UniversityofCambridge,Cambridge,United
Kingdom, 5Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, Texas, United States of America,
6DepartmentofPharmacology,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica
Abstract
Aberrant Rasactivityis ahallmarkofdiverse cancersanddevelopmental diseases. Unfortunately, conventionalefforts to
develop effective small molecule Ras inhibitors have met with limited success. We have developed a novel multi-level
computationalapproachtodiscoverpotentialinhibitorsofpreviouslyuncharacterizedallostericsites.Ourapproachcouples
bioinformatics analysis, advanced molecular simulations, ensemble docking and initial experimental testing of potential
inhibitors.Moleculardynamicssimulationhighlightedconservedallostericcouplingofthenucleotide-bindingswitchregion
withdistalregions,includingloop7andhelix5.Bioinformaticsmethodsidentifiednoveltransientsmallmoleculebinding
pocketsclosetotheseregionsandinthevicinityoftheconformationallyresponsiveswitchregion.Candidatebindersfor
these pockets were selected through ensemble docking of ZINC and NCI compound libraries. Finally, cell-based assays
confirmedourhypothesisthatthechosenbinderscaninhibitthedownstreamsignalingactivityofRas.Wethuspropose
thatthepredictedallostericsitesareviabletargetsforthedevelopmentandoptimizationofnewdru
您可能关注的文档
- Noncanonical MicroRNAs and Endogenous siRNAs in Lytic Infection of Murine Gammaherpesvirus 英文参考文献.doc
- Noncommunicable Diseases and Injuries in Latin America and the Caribbean Time for Action 英文参考文献.doc
- None of the Six SNPs of IL28B Could Predict Treatment Responses in Genotype 2 Chronic HCV Infected Patients by Propensity Score Matching Analysis 英文参考文献.doc
- Nonassociative Learning Promotes Respiratory Entrainment to Mechanical Ventilation 英文参考文献.doc
- Nonhuman Primate Models for HIV Cure Research 英文参考文献.doc
- Nondisjunction of a Single Chromosome Leads to Breakage and Activation of DNA Damage Checkpoint in G2 英文参考文献.doc
- Nonhuman Primate Models for SARS 英文参考文献.doc
- Noninvasive Cardiac Flow Assessment Using High Speed Magnetic Resonance Fluid Motion Tracking 英文参考文献.doc
- Nonlinear Fitness Landscape of a Molecular Pathway 英文参考文献.doc
- Noninvasive Visualization of the Activated αvβ3 Integrin in Cancer Patients by Positron Emission Tomography and [18F]Galacto-RGD 英文参考文献.doc
- Razer雷蛇Razer Phone RZ35-02150 用户指南 (Italian)说明书用户手册.pdf
- Razer雷蛇雷蛇飓兽 RZ06-01970 用户指南 (Spanish)说明书用户手册.pdf
- Razer雷蛇雷蛇雨林狼蛛 RZ03-0204x 用户指南 (Russian)说明书用户手册.pdf
- Razer雷蛇雷蛇幻影战狼 V2专业版 RZ06-04710 用户指南 (Korean)说明书用户手册.pdf
- Razer雷蛇雷蛇战斧 ATX 机箱 RC21-01420 Installation Guide (Russian)说明书用户手册.pdf
- Razer雷蛇雷蛇Xbox Pro 通用充电底座 RC21-01750 支持和常见问题解答 用户指南 (Japanese)说明书用户手册.pdf
- Razer雷蛇雷蛇噬魂金蝎V2 RZ03-0450x 用户指南 (繁体中文)说明书用户手册.pdf
- Razer雷蛇雷蛇利维坦巨兽V2 专业版 RZ05-04160 用户指南 (Russian)说明书用户手册.pdf
- Intel英特尔亚太地区的 AI 边缘:通过开放式混合云释放增长(Red Hat & Intel).pdf
- Razer雷蛇雷蛇风灵专业版 RZ38-0494 用户指南 (Russian)说明书用户手册.pdf
文档评论(0)