Continuous molecular fields models

Continuous Molecular Fields Approach Applied to Structure-Activity Modeling... 

In this section, we consider a new approach to building stracture-activity and structure-property models based on the use of continuous functions on space coordinates (called hereinafter continuous molecular fields) to represent molecular... 

Tables 13.5 and 13.6 summarize the results of building 1-SVM models on the basis of continuous molecular fields for HIV reverse transcriptase (HIVRT) and trypsin inhibitors. As follows from Table 13.5, the best performance for HIVRT is obtained by the model constracted using the steric kernel and resulting in an AUC value of 0.75. For this target, the use of a hnear combination of several kernels does not improve the AUC value. At the same time, for trypsin inhibitors, rather high AUC values (0.86-0.91) were obtained on the basis of individual models constructed with the use of all three kernels, which is likely due to their mutual correlation. However, for this target, the use of a linear combination of all kernels increases the AUC value up to 0.94.

Baskin II, Zhokhova NI (2013) The continuous molecular fields approach to building 3D-QSAR models. J Comput-Aided Mol Des 27(5) 427 2. doi 10.1007/sl0822-013-9656-4 CortesC, Vapnik V( 1995) Support-vector networks. Mach Leam 20(3) 273-297. doi 10.1007/ bf00994018... 

Scholkopf B, Platt JC, Shawe-Taylor J, Smola AJ, Williamson RC (2001) Estimating the support of a high-dimensional distribution. Neural Comput 13(7) 1443-1471 Karpov PV, Baskin II, Zhokhova NI, Zefirov NS (2011) Method of continuous molecular fields in the one-class classification task. Dokl Chem 440(2) 263-265 Karpov PV, Baskin II, ZhokhovaNI,Nawrozkij MB, ZefirovAN, Yablokov AS, Novakov lA, Zefirov NS (2011) One-class approach models for virtual screening of non-nucleoside HIV-1 reverse transcriptase inhibitors based on the concept of continuous molecular fields. Russ Chem Bull 60(ll) 2418-2424. doi 10.1007/slll72-011-0372-8... 

One tool for working toward this objective is molecular mechanics. In this approach, the bonds in a molecule are treated as classical objects, with continuous interaction potentials (sometimes called force fields) that can be developed empirically or calculated by quantum theory. This is a powerful method that allows the application of predictive theory to much larger systems if sufficiently accurate and robust force fields can be developed. Predicting the structures of proteins and polymers is an important objective, but at present this often requires prohibitively large calculations. Molecular mechanics with classical interaction potentials has been the principal tool in the development of molecular models of polymer dynamics. The ability to model isolated polymer molecules (in dilute solution) is well developed, but fundamental molecular mechanics models of dense systems of entangled polymers remains an important goal. 

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