染色质高级结构在基因调控中起到不可忽视的作用,染色质结构的形成与调控机制受到广泛关注。"相分离"理论近年来受到较多关注,异染色质与转录因子在其中的作用引人瞩目。但是,目前的相分离模型更关注结合因子与表观遗传性质,...染色质高级结构在基因调控中起到不可忽视的作用,染色质结构的形成与调控机制受到广泛关注。"相分离"理论近年来受到较多关注,异染色质与转录因子在其中的作用引人瞩目。但是,目前的相分离模型更关注结合因子与表观遗传性质,对DNA序列自身的作用理解尚较不充分。许多物种基因组的序列分布均具有多尺度的不均一性,仅基于Cp G岛(Cp G island,CGI)密度差异这一序列性质,就可以划分出基因、表观遗传、结构和转录性质都截然不同的高CGI密度"森林"和低CGI密度"草原"两种序列区域,体现了基因组自身的马赛克性。本文聚焦染色质结构的序列依赖性,讨论了染色质结构模型的研究进展,关注在序列几乎相同的不同细胞类型中的序列–结构关系及其功能调控,对发育、分化、衰老、疾病等多种过程的染色质结构变化进行了系统分析。针对基于序列的染色质相分离模型,对其物理驱动力进行了讨论,并在该模型的框架下基于相分离的物理特性,对温度、序列不均一性等物理因素对染色质结构可能造成的影响进行了探讨。展开更多
SPONGE(Simulation Package tOward Next GEneration molecular modeling)is a software package for molecular dynamics(MD)simulation of solution and surface molecular systems.In this version of SPONGE,the all-atom potential...SPONGE(Simulation Package tOward Next GEneration molecular modeling)is a software package for molecular dynamics(MD)simulation of solution and surface molecular systems.In this version of SPONGE,the all-atom potential energy functions used in AMBER MD packages are used by default and other all-atom/coarse-grained potential energy functions are also supported.SPONGE is designed to extend the timescale being approached in MD simulations by utilizing the latest CUDA-enabled graphical processing units(GPU)and adopting highly efficient enhanced sampling algorithms,such as integrated tempering,selective integrated tempering and enhanced sampling of reactive trajectories.It is highly modular and new algorithms and functions can be incorporated con veniently.Particularly,a specialized Python plugin can be easily used to perform the machine learning MD simulation with MindSpore,TensorFlow,PyTorch or other popular machine learning frameworks.Furthermore,a plugin of Finite-Element Method(FEM)is also available to handle metallic surface systems.All these advanced features increase the power of SPONGE for modeling and simulation of complex chemical and biological systems.展开更多
文摘染色质高级结构在基因调控中起到不可忽视的作用,染色质结构的形成与调控机制受到广泛关注。"相分离"理论近年来受到较多关注,异染色质与转录因子在其中的作用引人瞩目。但是,目前的相分离模型更关注结合因子与表观遗传性质,对DNA序列自身的作用理解尚较不充分。许多物种基因组的序列分布均具有多尺度的不均一性,仅基于Cp G岛(Cp G island,CGI)密度差异这一序列性质,就可以划分出基因、表观遗传、结构和转录性质都截然不同的高CGI密度"森林"和低CGI密度"草原"两种序列区域,体现了基因组自身的马赛克性。本文聚焦染色质结构的序列依赖性,讨论了染色质结构模型的研究进展,关注在序列几乎相同的不同细胞类型中的序列–结构关系及其功能调控,对发育、分化、衰老、疾病等多种过程的染色质结构变化进行了系统分析。针对基于序列的染色质相分离模型,对其物理驱动力进行了讨论,并在该模型的框架下基于相分离的物理特性,对温度、序列不均一性等物理因素对染色质结构可能造成的影响进行了探讨。
基金the National Key R&D Program of China(2017YFA0204702)the National Natural Science Foundation of China(21821004,21873007 and 21927901)CAAI-Huawei MindSpore Open Fund for financial support.
文摘SPONGE(Simulation Package tOward Next GEneration molecular modeling)is a software package for molecular dynamics(MD)simulation of solution and surface molecular systems.In this version of SPONGE,the all-atom potential energy functions used in AMBER MD packages are used by default and other all-atom/coarse-grained potential energy functions are also supported.SPONGE is designed to extend the timescale being approached in MD simulations by utilizing the latest CUDA-enabled graphical processing units(GPU)and adopting highly efficient enhanced sampling algorithms,such as integrated tempering,selective integrated tempering and enhanced sampling of reactive trajectories.It is highly modular and new algorithms and functions can be incorporated con veniently.Particularly,a specialized Python plugin can be easily used to perform the machine learning MD simulation with MindSpore,TensorFlow,PyTorch or other popular machine learning frameworks.Furthermore,a plugin of Finite-Element Method(FEM)is also available to handle metallic surface systems.All these advanced features increase the power of SPONGE for modeling and simulation of complex chemical and biological systems.
