Kumar Shashi, Seth Deepak, Deshpande Parag Arvind
Quantum and Molecular Engineering Laboratory, Department of Chemical Engineering, Indian Institute of Technology Kharagpur, Kharagpur, India.
Proteins. 2021 Apr;89(4):375-388. doi: 10.1002/prot.26022. Epub 2020 Nov 13.
The present study examined the structure and dynamics of the most active and thermostable carbonic anhydrase, SazCA, probed using molecular dynamics simulations. The molecular system was described by widely used biological force-fields (AMBER, CHARMM22, CHARMM36, and OPLS-AA) in conjunction with TIP3P water model. The comparison of molecular dynamics simulation results suggested AMBER to be a suitable choice to describe the structure and dynamics of SazCA. In addition to this, we also addressed the effect of temperature on the stability of SazCA. We performed molecular dynamics simulations at 313, 333, 353, 373, and 393 K to study the relationship between thermostability and flexibility in SazCA. The amino acid residues VAL98, ASN99, GLY100, LYS101, GLU145, and HIS207 were identified as the most flexible residues from root-mean-square fluctuations. The salt bridge analysis showed that ion-pairs ASP113-LYS81, ASP115-LYS81, ASP115-LYS114, GLU144-LYS143, and GLU144-LYS206, were responsible for the compromised thermal stability of SazCA.
本研究通过分子动力学模拟，研究了最具活性和热稳定性的碳酸酐酶SazCA的结构与动力学。分子系统由广泛使用的生物力场（AMBER、CHARMM22、CHARMM36和OPLS-AA）结合TIP3P水模型进行描述。分子动力学模拟结果的比较表明，AMBER是描述SazCA结构与动力学的合适选择。除此之外，我们还探讨了温度对SazCA稳定性的影响。我们在313、333、353、373和393 K下进行分子动力学模拟，以研究SazCA的热稳定性与柔韧性之间的关系。根据均方根波动，氨基酸残基VAL98、ASN99、GLY100、LYS101、GLU145和HIS207被确定为最具柔韧性的残基。盐桥分析表明，离子对ASP113-LYS81、ASP115-LYS81、ASP115-LYS114、GLU144-LYS143和GLU144-LYS206是导致SazCA热稳定性受损的原因。
