Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology , Thuwal , Saudi Arabia.
Monash Institute of Pharmaceutical Sciences, Monash University , Melbourne, VIC , Australia.
Front Bioeng Biotechnol. 2015 Jun 9;3:82. doi: 10.3389/fbioe.2015.00082. eCollection 2015.
Moonlighting functional centers within proteins can provide them with hitherto unrecognized functions. Here, we review how hidden moonlighting functional centers, which we define as binding sites that have catalytic activity or regulate protein function in a novel manner, can be identified using targeted bioinformatic searches. Functional motifs used in such searches include amino acid residues that are conserved across species and many of which have been assigned functional roles based on experimental evidence. Molecules that were identified in this manner seeking cyclic mononucleotide cyclases in plants are used as examples. The strength of this computational approach is enhanced when good homology models can be developed to test the functionality of the predicted centers in silico, which, in turn, increases confidence in the ability of the identified candidates to perform the predicted functions. Computational characterization of moonlighting functional centers is not diagnostic for catalysis but serves as a rapid screening method, and highlights testable targets from a potentially large pool of candidates for subsequent in vitro and in vivo experiments required to confirm the functionality of the predicted moonlighting centers.
蛋白质内的兼职功能中心可为其提供前所未有的功能。在这里，我们回顾了如何使用有针对性的生物信息学搜索来识别隐藏的兼职功能中心，我们将其定义为具有催化活性或以新颖方式调节蛋白质功能的结合位点。此类搜索中使用的功能基序包括在物种间保守的氨基酸残基，其中许多残基基于实验证据被赋予了功能作用。我们将以此种方式在植物中寻找环单核苷酸环化酶时所鉴定到的分子为例。当能够开发出良好的同源模型来在计算机上测试预测中心的功能时，这种计算方法的优势就会增强，这反过来又增加了所鉴定候选物执行预测功能的能力的可信度。对兼职功能中心的计算特征分析不能用于催化作用的诊断，但可用作快速筛选方法，并从潜在的大量候选物中突出可测试的靶标，以便随后进行体外和体内实验来确认预测的兼职中心的功能。
