Rapid Comparison of Protein Binding Site Surfaces with Property Encoded Shape Distributions
Rapid Comparison of Protein Binding Site Surfaces with Property Encoded Shape Distributions
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DOI：
10.1021/ci900317x
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发表时间：
2009-12-01
影响因子：
5.6
通讯作者：
Breneman, Curt M.
中科院分区：
文献类型：
--
作者：
Das, Sourav;Kokardekar, Arshad;Breneman, Curt M.
结合位点表面的形状和性质分布模式通常在功能蛋白质中是保守的，而不是显着地保守潜在的氨基酸残基。为了从配基的角度探索这些结合位点的相似性，创建了一种序列和折叠无关的方法来快速准确地比较由属性映射的三角Gauss-Connolly表面表示的蛋白质的结合位点。在这种模式下，每个结合位点表面的签名是通过计算其属性编码的形状分布(PESD)来产生的，PESD是一种特定属性在分子表面上处于另一特定距离的概率的度量。然后，签名之间的相似性被视为结合位点之间的相似性的度量。根据假设，即使在序列水平相似性很低的情况下，PESD方法也能快速检测到结合位点表面特征的高水平相似性。在涉及PDBBind 2005数据集的每个成员作为对集合的其余成员的查询的筛选实验中，在79.5%的情况下，PESD能够检索到具有相同的E.C.(酶委员会)编号作为最匹配的结合位点。将该方法在序列保守性较低的结合位点中检测相似性的能力与最新的结合位点比较方法进行了比较。
Patterns in shape and property distributions on the surface of binding sites are often conserved across functional proteins without significant conservation of the underlying amino-acid residues. To explore similarities of these sites from the viewpoint of a ligand, a sequence and fold-independent method was created to rapidly and accurately compare binding sites of proteins represented by property-mapped triangulated Gauss-Connolly Surfaces. Within this paradigm, signatures for each binding Site Surface are produced by calculating their property-encoded shape distributions (PESD), a Measure of the probability that a particular property will be at a specific distance to another on the Molecular surface. Similarity between the signatures call then be treated as a measure of similarity between binding sites. As postulated, the PESD method rapidly detected high levels of similarity in binding site surface characteristics even in cases where there was very low similarity Lit the sequence level. In a screening experiment involving each member of the PDBBind 2005 data set as a query against the rest of the set, PESD was able to retrieve a binding site with identical E.C. (Enzyme Commission) numbers as the top match in 79.5% of cases. The ability of the method in detecting similarity in binding sites with low sequence conservations was compared to state-of-the-art binding site comparison methods.