Tuberculosis Research and Treatment / 2013 / Article / Tab 2

Research Article

Design of Thymidine Analogues Targeting Thymidilate Kinase of Mycobacterium tuberculosis

Table 2

Complexation energy and its components for the training set of TMPKmt inhibitors: TMD1–TMD15.

Training seta comp
(g · mol−1)(kcal · mol−1)(kcal · mol−1)(kcal · mol−1)(kcal · mol−1)(μM)

TMD1 228 0 0 0 0 1020
TMD2 246 −3.942 3.537 −1.968−2.373 212
TMD3 354 −4.695 1.873 −2.196−5.017 33
TMD4 306 −1.631−3.514−1.742−6.887 5
TMD5 333 −5.880 1.212 −2.238−6.906 7
TMD6 258 −3.461 3.613 −1.371−1.220 238
TMD7 262 −5.157 7.239 −1.510 0.571 521
TMD8 242 3.496 −4.720 0.378 −0.847 230
TMD9 242 1.916 −1.255 0.786 1.447 1900
TMD10 256 −0.110−3.672−0.390−4.172 57
TMD11 258 −21.643 22.028 −3.572−3.187 45
TMD12 256 −1.323 0.216 −2.213−3.320 41
TMD13 272 3.727 −3.906−2.715−2.894 393
TMD14 270 −3.988 6.637 −3.934−1.286 156
TMD15 242 −6.706 9.914 −5.140−1.932 27

Validation set comp
[g · mol−1][kcal · mol−1][kcal · mol−1][kcal · mol−1][kcal · mol−1]

TMV1 −1.641−0.724−1.807−4.172 1.100
TMV2 −4.852 6.608 −0.372 1.385 0.899
TMV3 −4.166 2.479 −0.282−1.969 1.296
TMV4 2.350 −4.156−1.145−2.951 0.899
TMV5 −4.310 3.609 −0.527−1.228 1.164
TMV6 −3.999 2.689 −1.471−2.780 1.134

For the chemical structures of the training set of inhibitors see Table 1.
b is the molecular mass of the inhibitor.
c is the relative enthalpic contribution to the Gibbs free energy change related to the protease-inhibitor complex formation derived by molecular mechanics (MM): PR:TMDx TMDx PR:TMD1 TMD1 , TMD1—is the reference inhibitor;
d is the relative solvation Gibbs free energy contribution to the Gibbs free energy change related to protease-inhibitor complex formation: PR:TMDx TMDx PR:TMD1 TMD1 ;
e is the relative entropic contribution of the inhibitor to the Gibbs free energy related to protease-inhibitor complex formation: ;
f comp is the relative Gibbs free energy change related to the enzyme-inhibitor complex formation: .
g is the experimental TMPKmt inhibition constant obtained from [1517].
hRatio of predicted and experimental inhibition constants / was predicted from computed comp using the regression equation for TMPKmt shown in Table 3.