Gapsys Vytautas, de Groot Bert L
Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry , Am Fassberg 11, Göttingen, 37077, Germany.
J Chem Inf Model. 2017 Feb 27;57(2):109-114. doi: 10.1021/acs.jcim.6b00498. Epub 2017 Feb 16.
With the increase of available computational power and improvements in simulation algorithms, alchemical molecular dynamics based free energy calculations have developed into routine usage. To further facilitate the usability of alchemical methods for amino acid mutations, we have developed a web based infrastructure for obtaining hybrid protein structures and topologies. The presented webserver allows amino acid mutation selection in five contemporary molecular mechanics force fields. In addition, a complete mutation scan with a user defined amino acid is supported. The output generated by the webserver is directly compatible with the Gromacs molecular dynamics engine and can be used with any of the alchemical free energy calculation setup. Furthermore, we present a database of input files and precalculated free energy differences for tripeptides approximating a disordered state of a protein, of particular use for protein stability studies. Finally, the usage of the webserver and its output is exemplified by performing an alanine scan and investigating thermodynamic stability of the Trp cage mini protein. The webserver is accessible at http://pmx.mpibpc.mpg.de.
随着可用计算能力的提高和模拟算法的改进，基于炼金术分子动力学的自由能计算已发展成为常规应用。为了进一步促进炼金术方法在氨基酸突变方面的实用性，我们开发了一个基于网络的基础设施，用于获取杂合蛋白质结构和拓扑结构。所展示的网络服务器允许在五个当代分子力学力场中选择氨基酸突变。此外，还支持使用用户定义的氨基酸进行完整的突变扫描。网络服务器生成的输出与Gromacs分子动力学引擎直接兼容，可用于任何炼金术自由能计算设置。此外，我们还提供了一个输入文件数据库以及针对近似蛋白质无序状态的三肽预先计算的自由能差异，这对于蛋白质稳定性研究特别有用。最后，通过进行丙氨酸扫描和研究色氨酸笼状小蛋白质的热力学稳定性，举例说明了网络服务器的使用及其输出。该网络服务器可通过http://pmx.mpibpc.mpg.de访问。
