Abstract：
Fascin is a filamentous actin (F-actin) bundling protein, which cross-links F-actin into bundles and becomes an important component of filopodia on the cell surface. Fascin is overexpressed in many types of cancers. The mutation of fascin affects its ability to bind to F-actin and the progress of cancer. In this paper, we have studied the effects of residues of K22, K41, K43, K241, K358, K399, and K471 using molecular dynamics (MD) simulation. For the strong-effect residues, that is, K22, K41, K43, K358, and K471, our results show that the mutation of K to A leads to large values of root mean square fluctuation (RMSF) around the mutated residues, indicating those residues are important for the flexibility and thermal stability. On the other hand, based on residue cross-correlation analysis, alanine mutations of these residues reinforce the correlation between residues. Together with the RMSF data, the local flexibility is extended to the entire protein by the strong correlations to influence the dynamics and function of fascin. By contrast, for the mutants of K241A and K399A those do not affect the function of fascin, the RMSF data do not show significant differences compared with wild-type fascin. These findings are in a good agreement with experimental studies.
摘要：
Fascin是一种丝状肌动蛋白（F-actin）成束蛋白，它将F-肌动蛋白交联成束，并成为细胞表面丝状足的重要组成部分。Fascin在许多类型的癌症中过度表达。Fascin的突变影响其与F-肌动蛋白的结合能力和癌症的进展。在本文中,我们使用分子动力学（MD）模拟研究了K22，K41，K43，K241，K358，K399和K471残基的影响。对于强效应残留物，也就是说,K22，K41，K43，K358和K471，我们的结果表明，K到A的突变导致突变残基周围的均方根波动（RMSF）值很大，表明这些残留物对柔韧性和热稳定性很重要。另一方面,基于残差互相关分析，这些残基的丙氨酸突变增强了残基之间的相关性。连同RMSF数据，通过强烈的相关性将局部灵活性扩展到整个蛋白质，以影响fascin的动力学和功能。相比之下,对于K241A和K399A的突变体，它们不影响fascin的功能，与野生型fascin相比，RMSF数据没有显着差异。这些发现与实验研究非常吻合。
