analysis of x-ray structures of matrix metalloproteinases via chaotic map clustering分析x射线结构基质金属蛋白酶通过混沌映射聚类.pdfVIP

Giangreco et al. BMC Bioinformatics 2010, 11:500 /1471-2105/11/500 RESEARCH ARTICLE Open Access Analysis of X-ray Structures of Matrix Metalloproteinases via Chaotic Map Clustering 1 1* 1 2 2 2 Ilenia Giangreco , Orazio Nicolotti , Angelo Carotti , Francesco De Carlo , Gianfranco Gargano , Roberto Bellotti Abstract Background: Matrix metalloproteinases (MMPs) are well-known biological targets implicated in tumour progression, homeostatic regulation, innate immunity, impaired delivery of pro-apoptotic ligands, and the release and cleavage of cell-surface receptors. With this in mind, the perception of the intimate relationships among diverse MMPs could be a solid basis for accelerated learning in designing new selective MMP inhibitors. In this regard, decrypting the latent molecular reasons in order to elucidate similarity among MMPs is a key challenge. Results: We describe a pairwise variant of the non-parametric chaotic map clustering (CMC) algorithm and its application to 104 X-ray MMP structures. In this analysis electrostatic potentials are computed and used as input for the CMC algorithm. It was shown that differences between proteins reflect genuine variation of their electrostatic potentials. In addition, the analysis has been also extended to analyze the protein primary structures and the molecular shapes of the MMP co-crystallised ligands. Conclusions: The CMC algorithm was shown to be a valuable tool in knowledge acquisition and transfer from MMP structures. Based on the variation of electrostatic potentials, CMC was successful in analysing the MMP target family landscape and different subsites. The first investigation resulted in rational figure interpretation of both doma