Very fast empirical prediction and rationalization of protein pKa values

Proteins: Structure, Function and Bioinformatics - Tập 61 Số 4 - Trang 704-721 - 2005
Hui Li1, Andrew D. Robertson2, Jan H. Jensen1
1Department of Chemistry and Center for Biocatalysis and Bioprocessing, The University of Iowa, Iowa City, Iowa
2Department of Biochemistry, The University of Iowa, Iowa City, Iowa

Tóm tắt

AbstractA very fast empirical method is presented for structure‐based protein pKa prediction and rationalization. The desolvation effects and intra‐protein interactions, which cause variations in pKa values of protein ionizable groups, are empirically related to the positions and chemical nature of the groups proximate to the pKa sites. A computer program is written to automatically predict pKa values based on these empirical relationships within a couple of seconds. Unusual pKa values at buried active sites, which are among the most interesting protein pKa values, are predicted very well with the empirical method. A test on 233 carboxyl, 12 cysteine, 45 histidine, and 24 lysine pKa values in various proteins shows a root‐mean‐square deviation (RMSD) of 0.89 from experimental values. Removal of the 29 pKa values that are upper or lower limits results in an RMSD = 0.79 for the remaining 285 pKa values. Proteins 2005. © 2005 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

10.1021/ar00069a004

10.1002/prot.10174

10.1080/15216540211468

10.1021/bi9617724

10.1006/jmbi.2001.5009

10.1073/pnas.211436698

10.1110/ps.03114903

10.1021/bi9601565

10.1006/jmbi.1994.1301

10.1021/bi00496a010

10.1007/s002490050236

10.1002/prot.340150304

10.1016/S0006-3495(99)76868-2

10.1002/(SICI)1096-987X(19961115)17:14<1633::AID-JCC5>3.0.CO;2-M

10.1093/protein/8.3.243

10.1021/jp960111d

10.1002/prot.1053

10.1021/bi980187v

10.1021/bi992967p

10.1016/S0022-2836(02)01273-1

10.1007/978-94-009-5883-8

10.1002/prot.20032

Jeffrey GA, 1997, An introduction to hydrogen bonding

10.1107/S0108768189009195

10.1016/0022-2836(92)90260-Q

10.1093/nar/28.1.235

10.1016/S0969-2126(01)00192-7

10.1016/S0969-2126(96)00079-2

10.1021/ja01577a001

10.1021/bi025571d

Sundd M, 2002, Investigation of electrostatics in ubiquitin by mutagenesis and NMR, Biophys J, 82, 299a

10.1016/S0022-2836(03)00995-1

10.1016/S0006-3495(00)76411-3

Garcia‐Moreno B, 1998, Solvent penetration may be responsible for the high dielectric constant inside a protein, Biophys J, 74, A132

10.1016/S0301-4622(96)02238-7

10.1110/ps.4700102

10.1021/bi0119417

Spencer DS, 1998, The pK(a) of buried ionizable groups in staph nuclease: an experimental measure of the dielectric constant of a protein interior, Biophys J, 74, A170

10.1016/S0301-4622(02)00192-8

10.1002/prot.10332

10.1002/j.1460-2075.1986.tb04521.x

10.1002/prot.20032

10.1021/bi00183a034

10.1016/0022-2836(87)90679-6

10.1107/S0907444993005542

10.1021/bi00181a032

10.1006/jmbi.1994.1691

10.1038/297162a0

10.1107/S010876818300275X

10.1107/S0108767389009177

10.1021/bi961533g

10.1016/0300-9084(91)90169-2

10.1126/science.8278812

10.1021/jm960586t

10.1021/jm9602571

10.1126/science.2548279

10.1126/science.2686029

10.1021/bi962594h

10.1073/pnas.92.16.7337

10.1021/bi00375a036

10.1016/S0969-2126(96)00150-5

10.1006/jmbi.2000.3813

10.1016/0022-2836(92)90325-E

10.1016/0022-2836(85)90347-X

10.1021/bi00116a033

10.1016/0022-2836(92)90527-Q

10.1038/365464a0

10.1016/0022-2836(90)90313-B

10.1002/pro.5560010302

10.1107/S0907444901007703

10.1016/0014-5793(96)00697-7

10.1107/S0108768191003191

10.1021/bi960335m

10.1110/ps.9.7.1274

10.1074/jbc.270.10.5527

10.1107/S0567740882006153

10.1021/bi00203a006

10.1016/0022-2836(92)90841-7

Jia ZC, 1993, The 2.0‐Angstrom resolution structure of Escherichia coli histidine‐containing phosphocarrier protein Hpr—a redetermination, J Biol Chem, 268, 22490, 10.1016/S0021-9258(18)41556-6

10.1016/0022-2836(81)90125-X

10.1016/S0022-2836(05)80270-0

10.1021/bi9606105

10.1021/bi00013a021

10.1126/science.1709301

10.1002/prot.10177

10.1016/S0006-3495(02)73940-4

10.1021/bi049948m

10.1007/s002490100138

10.1515/BC.2003.010

10.1002/prot.1106

10.1021/bi980333x

10.1006/jmbi.2001.4767

10.1021/bi952299h

10.1110/ps.8.1.180

10.1038/nsb1196-946

10.1021/bi00098a024

Ido E, 1991, Kinetic‐studies of human‐immunodeficiency‐virus type‐1 protease and its active‐site hydrogen‐bond mutant A28s, J Biol Chem, 266, 24359, 10.1016/S0021-9258(18)54237-X

10.1021/bi00029a018

Wada A, 1976, The alpha‐helix as an eletric macrodipole, Adv Biophys, 9, 1

10.1006/jmbi.1995.0592

10.1073/pnas.88.5.2026

10.1021/bi981672t

10.1006/jmbi.1997.1080

10.1110/ps.0229903

10.1021/ja034956w

10.1021/bi0105429

Thông tin
Thông tin xuất bản

Proteins: Structure, Function and Bioinformatics

Tập 61 Số 4

704-721

Thông tin tác giả