非天然相互作用对均聚多肽链螺旋形成动力学过程的影响的计算机模拟研究

COMPUTER SIMULATION OF THE ROLE OF NON-NATIVE INTERACTIONS IN THE KINETIC PROCESS OF HELIX FORMATION FOR A HOMOPOLYPEPTIDE CHAIN

以螺旋结构的形成过程为研究对象,基于粗粒化的格子模型和动态蒙特卡罗模拟方法,初步探讨了非天然氢键相互作用对均聚多肽链螺旋折叠动力学过程的影响.研究发现,非天然氢键的引入虽然延缓了其热力学转变的发生,但也从整体上降低了折叠动力学过程的能垒,在某一特定温度之下,反而可以提高折叠速率.对其折叠路径分布的分析表明,非天然氢键可以减少慢速折叠路径的发生,而后者是导致折叠时间增加的主要因素.另一方面,比较特定温度下多肽链链构象及螺旋片断随时间的演化进程,发现非天然氢键在一定程度上影响了天然氢键的形成以及天然态构象的稳定存在,同时也加快了其部分解折叠过程.这说明,非天然相互作用的存在有利于蛋白质构象的快速动态调整,从而行使其相应的生物功能.

The role of non-native hydrogen bonding on the kinetic process of helix formation for a homopolypeptide chain was explored based on a coarse-grained lattice model and dynamic Monte Carlo simulation.It was found that,though postponing the thermodynamic helix-coil transition,non-native hydrogen bonding can decrease the energy barrier of the folding kinetic process,and further increased the folding rate below a specific temperature.The distribution of folding trajectories indicated that the slow folding trajectories were reduced with the inclusion of non-native interactions,which can evidently influence the folding time.On the other hand,the evolution of chain conformation and the length of helix segment were investigated,and the non-native hydrogen bonding was found to delay the formation of native hydrogen bond and weaken the stabilization of the corresponding native conformation,thus speeding up its unfolding process.Our research indicated that the occurrence of non-native interaction can offer a potential means for frequently dynamical adjusting of protein conformation so as to perform biological functions.