Castrignanò Tiziana, De Meo Paolo D'Onorio, Carrabino Danilo, Orsini Massimilano, Floris Matteo, Tramontano Anna
CASPUR, Consorzio Interuniversitario per le Applicazioni di Supercalcolo per Universita' e Ricerca, Via dei Tizii, 6/b, 5 I-00185 Rome, Italy.
BMC Bioinformatics. 2007 Mar 8;8 Suppl 1(Suppl 1):S6. doi: 10.1186/1471-2105-8-S1-S6.
One of the most interesting problems in molecular immunology is epitope mapping, i.e. the identification of the regions of interaction between an antigen and an antibody. The solution to this problem, even if approximate, would help in designing experiments to precisely map the residues involved in the interaction and could be instrumental both in designing peptides able to mimic the interacting surface of the antigen and in understanding where immunologically important regions are located in its three-dimensional structure. From an experimental point of view, both genetically encoded and chemically synthesised peptide libraries can be used to identify sequences recognized by a given antibody. The problem then arises of which region of a folded protein the selected peptides correspond to.
We have developed a method able to find the surface region of a protein that can be effectively mimicked by a peptide, given the structure of the protein and the maximum number of side chains deemed to be required for recognition. The method is implemented as a publicly available server. It can also find and report all peptide sequences of a specified length that can mimic the surface of a given protein and store them in a database. The immediate application of the server is the mapping of antibody epitopes, however the system is sufficiently flexible for allowing other questions to be asked, for example one can compare the peptides representing the surface of two proteins known to interact with the same macromolecule to find which is the most likely interacting region.
We believe that the MEPS server, available at http://www.caspur.it/meps, will be a useful tool for immunologists and structural and computational biologists. We plan to use it ourselves to implement a database of "surface mimicking peptides" for all proteins of known structure and proteins that can be reliably modelled by comparative modelling.
分子免疫学中最有趣的问题之一是表位作图，即确定抗原与抗体之间的相互作用区域。即使是近似地解决这个问题，也将有助于设计实验来精确绘制参与相互作用的残基图谱，并且在设计能够模拟抗原相互作用表面的肽以及理解免疫重要区域在其三维结构中的位置方面都可能发挥作用。从实验角度来看，遗传编码和化学合成的肽库都可用于鉴定给定抗体识别的序列。随之而来的问题是，所选肽对应于折叠蛋白的哪个区域。
我们开发了一种方法，给定蛋白质的结构以及认为识别所需的最大侧链数量，该方法能够找到可被肽有效模拟的蛋白质表面区域。该方法作为一个公开可用的服务器实现。它还可以找到并报告指定长度的所有能够模拟给定蛋白质表面的肽序列，并将它们存储在数据库中。该服务器的直接应用是抗体表位作图，然而该系统足够灵活，允许提出其他问题，例如，可以比较代表已知与同一大分子相互作用的两种蛋白质表面的肽，以找出最可能的相互作用区域。
