ON THE CALCULATION OF PK(A)S IN PROTEINS

被引:482
作者
YANG, AS [1 ]
GUNNER, MR [1 ]
SAMPOGNA, R [1 ]
SHARP, K [1 ]
HONIG, B [1 ]
机构
[1] COLUMBIA UNIV COLL PHYS & SURG,DEPT BIOCHEM & MOLEC BIOPHYS,630 W 168TH ST,NEW YORK,NY 10032
来源
PROTEINS-STRUCTURE FUNCTION AND GENETICS | 1993年 / 15卷 / 03期
关键词
TITRATION CURVES; ELECTROSTATICS; IONIZATION; ION PAIRS; SALT BRIDGES;
D O I
10.1002/prot.340150304
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This paper describes a general method to calculate the pK(a)s of ionizable groups in proteins. Electrostatic calculations are carried out using the finite difference Poisson-Boltzmann (FDPB) method. A formal treatment of the calculation of pK(a)s within the framework of the FDPB method is presented. The major change with respect to previous work is the specific incorporation of the complete charge distribution of both the neutral and charged forms of each ionizable group into the formalism. This is extremely important for the treatment of salt bridges. A hybrid statistical mechanical/Tanford-Roxby method, which is found to be significantly faster than previous treatments, is also introduced. This simplifies the problem of summing over the large number of possible ionization states for a complex poly-ion. Applications to BPTI and serine proteases suggest that the calculations can be quite reliable. However, the necessity of including bound waters in the treatment of the Asp-70 ... His-31 salt bridge in T4 lysozyme and experience with other proteins suggest that additional factors ultimately need to be considered in a comprehensive treatment of pK(a)s in proteins.
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页码:252 / 265
页数:14
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