PKAS OF IONIZABLE GROUPS IN PROTEINS - ATOMIC DETAIL FROM A CONTINUUM ELECTROSTATIC MODEL
PKAS OF IONIZABLE GROUPS IN PROTEINS - ATOMIC DETAIL FROM A CONTINUUM ELECTROSTATIC MODEL
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DOI：
10.1021/bi00496a010
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发表时间：
1990-11-06
期刊：
影响因子：
2.9
通讯作者：
KARPLUS, M
中科院分区：
文献类型：
--
作者：
BASHFORD, D;KARPLUS, M
采用宏观静电模型来计算溶菌酶中可滴定基团的pKa值。该模型利用详细的结构信息，并处理由永久部分电荷和可滴定电荷产生的溶剂化自能及相互作用。对四方晶系和三斜晶系的晶体结构都进行了分析。两种结构的计算都很好地重现了一半的实验观测到的pKa位移（21个中的11个）；这包括活性位点中Glu 35异常高的pKa值。对于超过一半的pKa值（21个中的13个），两种结构的结果之间存在较大差异（1 - 3.3个pK单位）。其中许多对应于计算有误的可滴定基团。由于在离子强度为0.1 M时，可滴定基团之间的德拜屏蔽导致非常高的有效介电常数（所有可滴定基团对的平均值约为900），近邻相互作用在pKa微扰中占主导地位。因此，pKa值对局部蛋白质构象的细节非常敏感，并且侧链的流动性很可能在决定观测到的pKa位移中起重要作用。
A macroscopic electrostatic model is used to calculate the pKa values of the titratable groups in lysozyme. The model makes use of detailed structural information and treats solvation self-energies and interactions arising from permanent partial charges and titratable charges. Both the tetragonal and triclinic crystal structures are analyzed. Half of the experimentally observed pKa shifts (11 out of 21) are well reproduced by calculations for both structures; this includes the unusually high pKa of Glu 35 in the active site. For more than half the pKa''s (13 out of 21), there is a large difference (1-3.3 pK units) between the results from the two structures. Many of these correspond to the titrating groups for which the calculations are in error. Since for an ionic strength of 0.1 M the Debye screening between titratable groups leads to a very high effective dielectric constant (the average value for all pairs of titrating groups is approximately 900), near-neighbor interactions dominate the pKa perturbations. Thus, the pKa values are very sensitive to the details of the local protein conformation, and it is likely that side-chain mobility has an important role in determining the observed pKa shifts.