ROLE OF ELECTROSTATIC SCREENING IN DETERMINING PROTEIN MAIN-CHAIN CONFORMATIONAL PREFERENCES
ROLE OF ELECTROSTATIC SCREENING IN DETERMINING PROTEIN MAIN-CHAIN CONFORMATIONAL PREFERENCES
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DOI：
10.1021/bi00003a008
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发表时间：
1995-01-24
期刊：
影响因子：
2.9
通讯作者：
MOULT, J
中科院分区：
文献类型：
--
作者：
AVBELJ, F;MOULT, J
氨基酸在α（R）-螺旋、β-折叠以及蛋白质和肽中的其他主链构象状态的倾向方面显示出显著变化。这些偏好的物理原因仍然存在争议。构象熵、空间因素和疏水效应都被认为是主要的潜在原因。在这项工作中，我们探讨了第四个因素，静电，在决定蛋白质分子的主链构象的作用。从实验蛋白质结构中导出的平均力势，用于评估蛋白质环境中残基的静电和其他相互作用的自由能。发现主链极性原子的局部和非理想静电相互作用对于确定残基的α（R）-螺旋状态和残基的其他主链构象状态的偏好是至关重要的。此外，局部和非局部静电相互作用的强度取决于静电屏蔽：溶剂和蛋白质基团。以与侧链体积和矮胖度相关的方式对该筛选进行残基特异性调制产生了一种模型，该模型与所观察到的蛋白质中残基构象分布和最近关于蛋白质稳定性的实验诱变数据拟合得比任何其他单一因素更好。
Amino acids display significant variation in propensity for the alpha(R)-helical, beta-sheet; and other main chain conformational states in proteins and peptides. The physical reason for these preferences remains controversial. Conformational entropy, steric factors, and the hydrophobic effect have all been advanced as the dominant underlying cause. Iii this work,we explore the role of a fourth factor, electrostatics, in determining the main chain conformation in protein molecules. Potentials of mean force derived from experimental protein structures ard used to evaluate the free energy of electrostatic and other interactions of a residue in a protein environment. The local and nonideal electrostatic interactions of main chain polar atoms are found to be crucial for determining the preferences of residues for the alpha(R)-helical state: and other main chain conformational states of a residue. Further, the strength of local and nonlocal electrostatic interactions is shown to depend on the electrostatic screening by:solvent and protein groups. Residue specific modulation of this screening in a manner related to side chain bulk and squatness produces a model that fits the observed distribution bf residue conformations in proteins and recent experimental mutagenesis data on protein stability better than any other single factor.