propka3.0, revision 182 2013-03-18 ------------------------------------------------------------------------------------------------------- -- -- -- PROPKA: A PROTEIN PKA PREDICTOR -- -- -- -- VERSION 1.0, 04/25/2004, IOWA CITY -- -- BY HUI LI -- -- -- -- VERSION 2.0, 11/05/2007, IOWA CITY/COPENHAGEN -- -- BY DELPHINE C. BAS AND DAVID M. ROGERS -- -- -- -- VERSION 3.0, xx/xx/2010, COPENHAGEN -- -- BY MATS H.M. OLSSON AND CHRESTEN R. SONDERGARD -- -- -- ------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------- References: Very Fast Empirical Prediction and Rationalization of Protein pKa Values Hui Li, Andrew D. Robertson and Jan H. Jensen PROTEINS: Structure, Function, and Bioinformatics 61:704-721 (2005) Very Fast Prediction and Rationalization of pKa Values for Protein-Ligand Complexes Delphine C. Bas, David M. Rogers and Jan H. Jensen PROTEINS: Structure, Function, and Bioinformatics 73:765-783 (2008) PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa predictions Mats H.M. Olsson, Chresten R. Sondergard, Michal Rostkowski, and Jan H. Jensen Journal of Chemical Theory and Computation, to be submitted (2010) ------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------- WARNING ! Propka3.0 is not identical to propka2.0 and does not work with ligands ------------------------------------------------------------------------------------------------------- --------- ----- ------ --------------------- -------------- -------------- -------------- DESOLVATION EFFECTS SIDECHAIN BACKBONE COULOMBIC RESIDUE pKa BURIED REGULAR RE HYDROGEN BOND HYDROGEN BOND INTERACTION --------- ----- ------ --------- --------- -------------- -------------- -------------- ASP 144 X 3.22 0 % 0.32 156 0.00 0 -0.17 ARG 151 X 0.00 XXX 0 X -0.29 ARG 151 X ASP 144 X -0.30 ARG 148 X 0.00 XXX 0 X -0.01 HIS 140 X ASP 144 X 0.00 XXX 0 X 0.00 XXX 0 X 0.18 ASP 147 X ASP 144 X 0.00 XXX 0 X 0.00 XXX 0 X -0.31 ARG 148 X ASP 147 X 3.02 0 % 0.43 240 0.00 0 -0.77 ARG 151 X 0.00 XXX 0 X -0.02 ARG 148 X ASP 147 X 0.00 XXX 0 X 0.00 XXX 0 X -0.08 HIS 140 X ASP 147 X 0.00 XXX 0 X 0.00 XXX 0 X -0.34 ARG 151 X ASP 167 X 3.00 0 % 0.39 229 0.00 0 -0.85 SER 222 X -0.34 ASP 167 X 0.00 XXX 0 X ASP 178 X 2.80 25 % 1.37 351 0.06 0 -0.85 TYR 128 X 0.00 XXX 0 X -0.06 LYS 185 X ASP 178 X -1.01 ARG 164 X 0.00 XXX 0 X -0.07 HIS 177 X ASP 178 X 0.00 XXX 0 X 0.00 XXX 0 X -0.44 ARG 164 X ASP 202 X 1.79 27 % 1.48 357 0.08 0 -0.78 TYR 149 X 0.00 XXX 0 X -0.47 ARG 156 X ASP 202 X -1.61 ARG 156 X 0.00 XXX 0 X 0.00 XXX 0 X ASP 202 X -0.70 TYR 157 X 0.00 XXX 0 X 0.00 XXX 0 X GLU 146 X 3.98 0 % 0.45 266 0.00 0 -0.85 THR 201 X 0.00 XXX 0 X -0.08 LYS 204 X GLU 146 X 0.00 XXX 0 X 0.00 XXX 0 X -0.04 ARG 208 X GLU 152 X 4.67 0 % 0.17 216 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.00 XXX 0 X GLU 196 X 4.56 0 % 0.06 99 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.00 XXX 0 X GLU 200 X 4.68 0 % 0.09 141 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.08 GLU 146 X GLU 207 X 4.85 15 % 0.41 323 0.06 0 0.00 XXX 0 X 0.00 XXX 0 X -0.12 HIS 177 X GLU 211 X 5.29 26 % 0.73 355 0.18 0 0.00 XXX 0 X 0.00 XXX 0 X -0.12 ARG 208 X GLU 221 X 4.73 0 % 0.15 211 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.08 ASP 167 X C- 226 X 2.69 0 % 0.24 154 0.00 0 -0.75 SER 170 X 0.00 XXX 0 X 0.00 XXX 0 X HIS 140 X 6.28 0 % -0.24 174 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X -0.07 ARG 208 X HIS 140 X 0.00 XXX 0 X 0.00 XXX 0 X 0.01 ASP 144 X HIS 140 X 0.00 XXX 0 X 0.00 XXX 0 X 0.08 ASP 147 X HIS 177 X 6.38 0 % -0.27 275 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X -0.04 LYS 185 X HIS 177 X 0.00 XXX 0 X 0.00 XXX 0 X 0.07 ASP 178 X HIS 177 X 0.00 XXX 0 X 0.00 XXX 0 X 0.12 GLU 207 X HIS 187 X 6.38 0 % -0.12 165 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.00 XXX 0 X CYS 179 X 99.99 0 % 0.00 0 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.00 XXX 0 X CYS 214 X 99.99 0 % 0.00 0 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.00 XXX 0 X TYR 128 X 11.69 11 % 0.76 312 0.00 0 -0.11 ARG 164 X 0.00 XXX 0 X -0.30 ARG 164 X TYR 128 X 0.85 ASP 178 X 0.00 XXX 0 X 0.04 TYR 169 X TYR 128 X 0.00 XXX 0 X 0.00 XXX 0 X 0.45 ASP 178 X TYR 149 X 12.03 19 % 1.41 334 0.00 0 -0.07 ARG 156 X -0.35 THR 199 X 0.03 GLU 146 X TYR 149 X 0.78 ASP 202 X 0.00 XXX 0 X 0.03 GLU 152 X TYR 149 X 0.00 XXX 0 X 0.00 XXX 0 X -0.29 ARG 156 X TYR 149 X 0.00 XXX 0 X 0.00 XXX 0 X 0.02 TYR 155 X TYR 149 X 0.00 XXX 0 X 0.00 XXX 0 X 0.47 ASP 202 X TYR 150 X 11.68 41 % 1.80 396 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X -0.07 ARG 136 X TYR 150 X 0.00 XXX 0 X 0.00 XXX 0 X 0.05 ASP 147 X TYR 150 X 0.00 XXX 0 X 0.00 XXX 0 X -0.10 ARG 208 X TYR 155 X 10.19 0 % 0.38 228 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X -0.00 ARG 136 X TYR 155 X 0.00 XXX 0 X 0.00 XXX 0 X 0.03 GLU 152 X TYR 155 X 0.00 XXX 0 X 0.00 XXX 0 X -0.15 ARG 156 X TYR 155 X 0.00 XXX 0 X 0.00 XXX 0 X 0.02 ASP 202 X TYR 155 X 0.00 XXX 0 X 0.00 XXX 0 X -0.09 LYS 194 X TYR 157 X 13.42 48 % 2.27 416 0.00 0 -0.28 ARG 156 X 0.00 XXX 0 X 0.01 GLU 146 X TYR 157 X 0.70 ASP 202 X 0.00 XXX 0 X -0.43 ARG 156 X TYR 157 X 0.00 XXX 0 X 0.00 XXX 0 X 0.42 TYR 149 X TYR 157 X 0.00 XXX 0 X 0.00 XXX 0 X 0.14 TYR 150 X TYR 157 X 0.00 XXX 0 X 0.00 XXX 0 X 0.03 TYR 155 X TYR 157 X 0.00 XXX 0 X 0.00 XXX 0 X 0.55 ASP 202 X TYR 162 X 10.28 0 % 0.41 247 0.00 0 -0.12 GLN 186 X 0.00 XXX 0 X 0.00 XXX 0 X TYR 163 X 11.07 25 % 0.83 350 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.02 ASP 167 X TYR 163 X 0.00 XXX 0 X 0.00 XXX 0 X 0.21 GLU 221 X TYR 169 X 9.93 0 % 0.49 245 0.00 0 -0.56 ASN 173 X 0.00 XXX 0 X -0.18 ARG 164 X TYR 169 X 0.00 XXX 0 X 0.00 XXX 0 X 0.18 ASP 178 X TYR 218 X 10.86 13 % 0.72 319 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.00 GLU 211 X TYR 218 X 0.00 XXX 0 X 0.00 XXX 0 X 0.13 TYR 225 X TYR 225 X 10.20 0 % 0.15 202 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.05 C- 226 X TYR 226 X 10.14 0 % 0.02 52 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.12 C- 226 X LYS 185 X 10.16 0 % -0.40 227 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X -0.00 ARG 164 X LYS 185 X 0.00 XXX 0 X 0.00 XXX 0 X 0.06 ASP 178 X LYS 194 X 10.32 0 % -0.21 212 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X -0.05 ARG 136 X LYS 194 X 0.00 XXX 0 X 0.00 XXX 0 X -0.01 ARG 156 X LYS 194 X 0.00 XXX 0 X 0.00 XXX 0 X 0.09 TYR 155 X LYS 204 X 10.36 0 % -0.13 212 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.08 GLU 146 X LYS 204 X 0.00 XXX 0 X 0.00 XXX 0 X -0.10 ARG 208 X LYS 220 X 10.40 0 % -0.10 172 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.00 XXX 0 X ARG 136 X 11.85 16 % -0.73 327 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.07 TYR 150 X ARG 136 X 0.00 XXX 0 X 0.00 XXX 0 X 0.00 TYR 155 X ARG 148 X 12.74 0 % -0.29 137 0.00 0 0.30 ASP 144 X 0.00 XXX 0 X 0.02 ASP 147 X ARG 148 X 0.00 XXX 0 X 0.00 XXX 0 X -0.11 ARG 151 X ARG 148 X 0.00 XXX 0 X 0.00 XXX 0 X 0.31 ASP 144 X ARG 151 X 13.69 0 % -0.38 177 0.00 0 0.17 ASP 144 X 0.00 XXX 0 X 0.29 ASP 144 X ARG 151 X 0.77 ASP 147 X 0.00 XXX 0 X 0.34 ASP 147 X ARG 156 X 14.56 18 % -1.23 332 0.00 0 0.07 TYR 149 X 0.00 XXX 0 X 0.29 TYR 149 X ARG 156 X 0.28 TYR 157 X 0.00 XXX 0 X 0.15 TYR 155 X ARG 156 X 1.61 ASP 202 X 0.00 XXX 0 X 0.43 TYR 157 X ARG 156 X 0.00 XXX 0 X 0.00 XXX 0 X 0.47 ASP 202 X ARG 164 X 13.94 5 % -0.59 294 0.00 0 0.11 TYR 128 X 0.00 XXX 0 X 0.30 TYR 128 X ARG 164 X 1.01 ASP 178 X 0.00 XXX 0 X 0.18 TYR 169 X ARG 164 X 0.00 XXX 0 X 0.00 XXX 0 X 0.44 ASP 178 X ARG 208 X 12.01 18 % -0.74 333 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X 0.04 GLU 146 X ARG 208 X 0.00 XXX 0 X 0.00 XXX 0 X 0.10 TYR 150 X ARG 208 X 0.00 XXX 0 X 0.00 XXX 0 X 0.12 GLU 211 X N+ 124 X 7.87 0 % -0.10 84 0.00 0 0.00 XXX 0 X 0.00 XXX 0 X -0.03 LYS 185 X -------------------------------------------------------------------------------------------------------- SUMMARY OF THIS PREDICTION RESIDUE pKa pKmodel ligand atom-type ASP 144 X 3.22 3.80 ASP 147 X 3.02 3.80 ASP 167 X 3.00 3.80 ASP 178 X 2.80 3.80 ASP 202 X 1.79 3.80 GLU 146 X 3.98 4.50 GLU 152 X 4.67 4.50 GLU 196 X 4.56 4.50 GLU 200 X 4.68 4.50 GLU 207 X 4.85 4.50 GLU 211 X 5.29 4.50 GLU 221 X 4.73 4.50 C- 226 X 2.69 3.20 HIS 140 X 6.28 6.50 HIS 177 X 6.38 6.50 HIS 187 X 6.38 6.50 CYS 179 X 99.99 99.99 CYS 214 X 99.99 99.99 TYR 128 X 11.69 10.00 TYR 149 X 12.03 10.00 TYR 150 X 11.68 10.00 TYR 155 X 10.19 10.00 TYR 157 X 13.42 10.00 TYR 162 X 10.28 10.00 TYR 163 X 11.07 10.00 TYR 169 X 9.93 10.00 TYR 218 X 10.86 10.00 TYR 225 X 10.20 10.00 TYR 226 X 10.14 10.00 LYS 185 X 10.16 10.50 LYS 194 X 10.32 10.50 LYS 204 X 10.36 10.50 LYS 220 X 10.40 10.50 ARG 136 X 11.85 12.50 ARG 148 X 12.74 12.50 ARG 151 X 13.69 12.50 ARG 156 X 14.56 12.50 ARG 164 X 13.94 12.50 ARG 208 X 12.01 12.50 N+ 124 X 7.87 8.00 -------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------- Free energy of folding (kcal/mol) as a function of pH (using neutral reference) 0.00 2.17 1.00 2.06 2.00 1.35 3.00 -1.08 4.00 -4.16 5.00 -4.47 6.00 -4.13 7.00 -4.37 8.00 -4.52 9.00 -4.28 10.00 -2.21 11.00 2.74 12.00 6.99 13.00 10.33 14.00 13.53 The pH of optimum stability is 4.6 for which the free energy is -4.6 kcal/mol at 298K The free energy is within 80 % of maximum at pH 3.8 to 9.4 The free energy is positive in the range 3.8 - 9.4 Protein charge of folded and unfolded state as a function of pH pH unfolded folded 0.00 14.00 13.98 1.00 13.98 13.80 2.00 13.84 12.82 3.00 12.71 10.20 4.00 8.38 7.02 5.00 2.90 3.34 6.00 0.52 0.47 7.00 -1.36 -1.53 8.00 -2.53 -2.56 9.00 -4.02 -3.48 10.00 -9.47 -6.66 11.00 -16.22 -12.38 12.00 -19.21 -16.81 13.00 -22.53 -19.84 14.00 -23.81 -22.12 The pI is 6.20 (folded) and 6.27 (unfolded)