同、异三聚体Ⅰ型胶原生物力学响应的分子动力学模拟

Molecular dynamics simulation of biomechanical response of homotrimeric and heterotrimeric type Ⅰ collagen

成骨不全症(osteogenesis imperfecta, OI)是一种遗传性的结缔组织疾病,主要由Ⅰ型胶原发生突变所造成。运用分子动力学模拟方法研究了同、异三聚体胶原分子的力学响应,得出突变Ⅰ型胶原与成骨不全症的相关性。通过创建真实小鼠序列的同、异三聚体两种Ⅰ型胶原三螺旋模型,利用分子动力学模拟软件包GROMACS对同、异三聚体胶原通过拉伸分子动力学(steered molecular dynamics, SMD)进行了在外力作用下的力学响应分析。模拟结果显示:(1)在结构方面,同三聚体胶原分子端到端的距离和均方根偏差(root mean square displacement, RMSD)的波动变化更大;(2)在力学响应方面,突变后的胶原力学属性发生了明显改变,结构稳定性降低,刚度更弱。最终导致胶原自组装形成的骨组织发生改变,引发成骨不全症。

Osteogenesis imperfecta(OI) is an inherited connective tissue disorder mainly caused by mutations in type Ⅰ collagen, and molecular dynamics simulations have been used to study the mechanical response of homo-and heterotrimeric collagen molecules to derive the correlation between mutant type Ⅰ collagen and osteogenesis imperfecta. By creating two triple helical models of type Ⅰ collagen that are homo-and heterotrimeric with the authentic mouse sequence, the mechanoresponse of homo-and heterotrimeric collagen to external forces by means of the molecular dynamics(SMD) simulation package GROMACS is analyzed. The simulation results showed that:(1) in terms of structure, the end-to-end distance as well as the root mean square deviation(RMSD) of the homotrimeric collagen molecules fluctuated more;(2) In terms of mechanical response, collagen mechanical properties are significantly altered upon mutation, with structural stability reduced concomitantly and weaker stiffness. Altered bone organization, which ultimately leads to the formation of collagen self-assembly and triggers osteogenesis imperfecta.