【摘 要】
：
Calcium-activated chloride channels (CaCCs) play important roles in many physiological processes which is dependent on the normal gating modulated by calciu
【机 构】
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KeyLaboratoryofMolecularBiophysics,HebeiProvince,InstituteofBiophysics,SchoolofSciences,HebeiUnivers
【出 处】
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第三届全国计算生物学与生物信息学学术会议
论文部分内容阅读
Calcium-activated chloride channels (CaCCs) play important roles in many physiological processes which is dependent on the normal gating modulated by calcium ions.Dysfunction of CaCCs will induce series of diseases.To understand the molecular mechanism of calcium dependent gating of CaCCs and investigate specific modulators of CaCCs,the authors combined molecular simulation with biological experiments,determined the calcium binding domain and identified a novel natural activator of TMEM16A from traditional Chinese medicines (TCM).First,we proposed a computational approach which combined the fragment homology modeling with molecular dynamics simulation.The computational method identified 43 from 49 Ca2+-binding sites.Then we moved to identify the calcium binding domain in the CaCCs and determined that the E447 binds with calcium ions by directly interacting the ion.At last,we discovered a novel activator,Ginsenoside Rb1,which can activate the CaCCs/TMEM16A channels in a Ca2+ independent way.The EC50 for Ginsenoside Rbl at +80mV is 38.4±2μM.Finally,we certified the effectiveness of the Ginsenoside Rb 1 at tissue level through isolated guinea pig ileum tension experiment.The data show that Ginsenoside Rb1 strengthens the contraction of guinea pig ileum which can be eliminated by CaCCinh-A01,a specific inhibitor of TMEM16A.
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