Quantum and Molecular Engineering Laboratory, Department of Chemical Engineering, Indian Institute of Technology Kharagpur, Kharagpur, India.
J Biomol Struct Dyn. 2023;41(21):12363-12371. doi: 10.1080/07391102.2023.2175259. Epub 2023 Feb 6.
Maintaining the protein stability upon mutation is a challenging task in protein engineering. In the present computational study, we induced a single point Gly100Ala mutation in SazCA and examined the factors governing the stability and flexibility of the mutated form, and compared it to that of the wildtype using molecular dynamics simulations. We observed higher structural stability and lesser residual mobility in the mutated SazCA. Improved H-bonding due to Gly100Ala was observed. Ala100 was responsible for the increased helical contents in the mutated SazCA while Gly100 compromised the secondary structure contents in the wildtype. A strong network of salt bridges and high local ordering of the solvent molecules at the protein surface contributed to the enhanced stability of the mutated protein. Our simulations conclusively highlight Gly100Ala mutation as a step towards designing a more robust and thermostable SazCA.Communicated by Ramaswamy H. Sarma.
在蛋白质工程中，维持蛋白质的稳定性是一项具有挑战性的任务。在本计算研究中，我们在 SazCA 中诱导了单点 Gly100Ala 突变，并使用分子动力学模拟研究了控制突变形式稳定性和柔韧性的因素，并将其与野生型进行了比较。我们观察到突变 SazCA 的结构稳定性更高，剩余的移动性更小。观察到由于 Gly100Ala 而导致的更好的氢键形成。Ala100 负责增加突变 SazCA 中的螺旋含量，而 Gly100 则破坏野生型中的二级结构含量。在蛋白质表面，盐桥的强网络和溶剂分子的高局部有序性有助于增强突变蛋白的稳定性。我们的模拟结论性地强调 Gly100Ala 突变是设计更稳健和热稳定的 SazCA 的一步。由 Ramaswamy H. Sarma 传达。
