ForceConstantAnalysis_RawData

we analyzed structural stability of the regulatory regions in different functional states of the ErbB kinases and characterized mutation-induced changes in stability profiles that may be relevant for activation mechanisms. For this analysis, we employed a number of complementary approaches, including the force constant profiling of residue connectivity, the contact network analysis of residue closeness, the relative solvent accessibility (RSA) evaluation of local residue environment, and the network-based analysis of local contact density. In the ensemble-based force constant analysis, the equilibrium fluctuations of the mean distance between each residue and the rest of the protein were converted into force constants that measure the energy cost of the residue displacement during equilibrium simulations. The high force constants are typically associated with structurally stable residues that display small fluctuations in their distances to other residues and often correspond to highly connect and effectively communicating rigid sites. Previous studies have linked structural stability of functionally important residues with their high connectivity, particularly indicating that catalytic and binding site residues typically have high force constant values, which reflects functional constraints imposed on their movement. Abrupt changes between maxima and minima in the force constant profiles may be associated with the regions bridging structurally rigid and flexible regions, often pointing to the hinge sites. The hypothesis tested in our analysis is that the R-spine residues could effectively mediate structural stability and allosteric interactions via regulatory regions. The analysis revealed that high force constant residues in the catalytic domain are assembled near the αC-helix, αE-helix and αF-helix regions suggesting that structural stability of these structural elements may be critical for allosteric coupling between regulatory regions本研究分析了ErbB激酶（ErbB kinases）不同功能状态下调节区域的结构稳定性，并表征了突变诱导的稳定性图谱变化，该变化可能与激活机制相关。为此，我们采用了多种互补分析方法，包括残基连接性的力常数（force constant）图谱分析、残基紧密性的接触网络分析、局部残基环境的相对溶剂可及性（relative solvent accessibility, RSA）评估，以及基于网络的局部接触密度分析。在基于集合的力常数分析中，我们将每个残基与蛋白质其余部分之间的平均距离的平衡波动转换为力常数，该常数用于衡量平衡模拟过程中残基位移的能量代价。高力常数通常对应结构稳定的残基，这类残基与其他残基的距离波动较小，且多属于高度连接且高效通讯的刚性位点。既往研究已将功能重要残基的结构稳定性与其高连接性相关联，尤其指出催化位点与结合位点的残基通常具有较高的力常数值，这反映了对其运动施加的功能约束。力常数图谱中极大值与极小值之间的剧烈变化通常对应连接刚性与柔性区域的过渡区域，往往指向铰链位点。本研究检验的假说为：R-spine残基（R-spine residues）可通过调节区域有效介导结构稳定性与变构相互作用。分析结果显示，催化结构域内的高力常数残基聚集于αC螺旋（αC-helix）、αE螺旋（αE-helix）与αF螺旋（αF-helix）区域附近，表明这些结构元件的结构稳定性可能对调节区域之间的变构偶联至关重要。