UT-ORNL Graduate School of Genome Science and Technology, Knoxville, Tennessee 37996, USA.
Department of Mathematics, Rutgers University, Piscataway, New Jersey 08854, USA.
J Chem Phys. 2018 Jan 14;148(2):025101. doi: 10.1063/1.5004141.
We have developed a method to capture the essential conformational dynamics of folded biopolymers using statistical analysis of coarse-grained segment-segment contacts. Previously, the residue-residue contact analysis of simulation trajectories was successfully applied to the detection of conformational switching motions in biomolecular complexes. However, the application to large protein systems (larger than 1000 amino acid residues) is challenging using the description of residue contacts. Also, the residue-based method cannot be used to compare proteins with different sequences. To expand the scope of the method, we have tested several coarse-graining schemes that group a collection of consecutive residues into a segment. The definition of these segments may be derived from structural and sequence information, while the interaction strength of the coarse-grained segment-segment contacts is a function of the residue-residue contacts. We then perform covariance calculations on these coarse-grained contact matrices. We monitored how well the principal components of the contact matrices is preserved using various rendering functions. The new method was demonstrated to assist the reduction of the degrees of freedom for describing the conformation space, and it potentially allows for the analysis of a system that is approximately tenfold larger compared with the corresponding residue contact-based method. This method can also render a family of similar proteins into the same conformational space, and thus can be used to compare the structures of proteins with different sequences.
我们开发了一种方法，通过对粗粒度片段-片段接触进行统计分析，来捕捉折叠生物聚合物的基本构象动力学。以前，模拟轨迹的残基残基接触分析已成功应用于生物分子复合物中构象切换运动的检测。然而，使用残基接触的描述来应用于大型蛋白质系统（大于 1000 个氨基酸残基）是具有挑战性的。此外，基于残基的方法不能用于比较具有不同序列的蛋白质。为了扩展该方法的范围，我们测试了几种粗粒化方案，即将一系列连续的残基组合成一个片段。这些片段的定义可以来源于结构和序列信息，而粗粒化片段-片段接触的相互作用强度是残基-残基接触的函数。然后，我们对这些粗粒化接触矩阵进行协方差计算。我们监测了使用各种渲染函数时接触矩阵的主成分保持得有多好。新方法被证明有助于减少描述构象空间的自由度，并且它可能允许分析与相应的基于残基接触的方法相比大约大十倍的系统。该方法还可以将一组相似的蛋白质渲染到相同的构象空间中，因此可用于比较具有不同序列的蛋白质的结构。
