Correction to intrinsic energy landscapes of amino acid side-chains.
Correction to intrinsic energy landscapes of amino acid side-chains.
复制标题
修正氨基酸侧链的内在能量景观。
DOI：
10.1021/ci300301x
复制
发表时间：
2012
影响因子：
5.6
通讯作者：
MackerellJr,AlexanderD
中科院分区：
文献类型：
--
作者：
Zhu,Xiao;Lopes,PedroEM;Shim,Jihyun;MackerellJr,AlexanderD
氨基酸侧链构象性质影响蛋白质的整体结构和动力学性质，从而影响其生物学功能。在这项研究中，量子力学（QM）势能面的旋转侧链的χ 1和χ 2扭转的二肽在alphaR，β，和alphaL骨架构象进行了计算。QM能量表面提供了每个氨基酸侧链的内在构象性质的广泛观点。通过对高分辨率晶体结构的概率分布的QM能面与χ 1和χ 2自由能面的比较，研究了内禀能决定侧链取向的程度.一般来说，调查概率最大值以QM表面的最小值为中心，如对于sp3（或对于Asn、Phe、Trp和Tyr的χ 2为sp2）原子中心所预期的，氨基酸之间在最小值的能量中发生强烈变化，表明旋转异构体偏好的内在差异。QM和调查数据之间的高相关性被发现的疏水性侧链，除蛋氨酸，这表明其构象分布的蛋白质和溶液环境的影响最小。相反，极性或带电侧链的低相关性表明环境在稳定本质上不受欢迎的构象中起主导作用。数据还将His和Trp中的非旋转异构体的存在与主链的有利相互作用联系起来。结果还表明，苯丙氨酸和酪氨酸的侧链的内在能量可能在蛋白质的折叠和稳定性中发挥重要作用。关于内在侧链能量学是否可以影响骨架偏好的分析确定了α L骨架构象中残基的强相关性。有人建议，这种相关性反映了固有的不稳定性的α L骨干，这样的假设，这种骨干构象是促进固有的有利的侧链构象。总之，我们的结果提供了一个广泛的概述的氨基酸侧链的构象特性和QM数据可用作力场优化的目标数据。
Amino acid side-chain conformational properties influence the overall structural and dynamic properties of proteins and, therefore, their biological functions. In this study, quantum mechanical (QM) potential energy surfaces for the rotation of side-chain χ1and χ2torsions in dipeptides in the alphaR, beta, and alphaL backbone conformations were calculated. The QM energy surfaces provide a broad view of the intrinsic conformational properties of each amino acid side-chain. The extent to which intrinsic energetics dictates side-chain orientation was studied through comparisons of the QM energy surfaces with χ1and χ2free energy surfaces from probability distributions obtained from a survey of high resolution crystal structures. In general, the survey probability maxima are centered in minima of the QM surfaces as expected for sp3(or sp2for χ2of Asn, Phe, Trp, and Tyr) atom centers with strong variations between amino acids occurring in the energies of the minima indicating intrinsic differences in rotamer preferences. High correlations between the QM and survey data were found for hydrophobic side-chains except Met, suggesting minimal influence of the protein and solution environments on their conformational distributions. Conversely, low correlations for polar or charged side-chains indicate a dominant role of the environment in stabilizing conformations that are not intrinsically favored. Data also link the presence of off-rotamers in His and Trp to favorable interactions with the backbone. Results also suggest that the intrinsic energetics of the side-chains of Phe and Tyr may play important roles in protein folding and stability. Analyses on whether intrinsic side-chain energetics can influence backbone preference identified a strong correlation for residues in the alphaL backbone conformation. It is suggested that this correlation reflects the intrinsic instability of the alphaL backbone such that assumption of this backbone conformation is facilitated by intrinsically favorable side-chain conformations. Together our results offer a broad overview of the conformational properties of amino acid side-chains and the QM data may be used as target data for force field optimization.