Mutations in Valosin-containing protein (VCP) have been implicated in the pathology linked to inclusion body myopathy, paget disease of bone and frontotemporal dementia (IBMPFD). VCP is an essential component of AAA-ATPase superfamily involved in various cellular functions. Advanced In-silico analysis was performed using prediction based servers to determine the most deleterious mutation. Molecular dynamics simulation was used to study the protein dynamics at atomic level. Molecular docking was used to study the effect of mutation on ATP/ADP transition in the kinase domain. This ATPase of 806 amino acids has four domains: N-terminal domain, C-terminal domain and two ATPase domains D1 and D2 and each of these domains have a distinct role in its functioning. The mutations in VCP protein are distributed among regions known as hotspots, one such hotspot is codon 155. Three missense mutations reported in this hotspot are R155C, R155H and R155P. Potentiality of the deleteriousness calculated using server based prediction models reveal R155C mutation to be the most deleterious. The atomic insight into the effect of mutation by molecular dynamics simulation revealed major conformational changes in R155C variants ATP binding site in D1 domain. The nucleotide-binding mode at the catalytic pocket of VCP and its three variants at codon 155 showed change in the structure, which affects the ATP–ADP transition kinetics in all the three variants.

包含Valosin的蛋白质 （VCP）的突变与涉及包涵体肌病，骨骼的Paget病和额颞痴呆（IBMPFD）有关。VCP是涉及各种细胞功能的AAA-ATPase超家族的重要组成部分。先进的计算机使用基于预测的服务器进行分析，以确定最有害的突变。分子动力学模拟被用来研究原子水平的蛋白质动力学。分子对接用于研究突变对激酶域中ATP / ADP过渡的影响。该806个氨基酸的ATPase具有四个结构域：N末端结构域，C末端结构域和两个ATPase结构域D1和D2，这些结构域中的每一个在其功能中均具有不同的作用。VCP蛋白中的突变分布在称为热点的区域之间，此类热点之一是密码子155。在该热点中报告的三个错义突变是R155C，R155H和R155P。使用基于服务器的预测模型计算得出的有害性潜力表明R155C突变是最有害的。通过分子动力学模拟对突变影响的原子洞察力揭示了D1域中R155C变体ATP结合位点的主要构象变化。VCP及其三个变体在155位密码子的催化口袋处的核苷酸结合模式显示出结构变化，这影响了所有三个变体中ATP-ADP的转变动力学。