QSPR Prediction of Lipophilicity for Organic Compounds Using Random Forest Technique on the Basis of Simplex Representation of Molecular Structure.

The relationship between the octanol-water partition coefficient for more than twelve thousand organic compounds and their structures was investigated using a QSPR approach based on Simplex Representation of Molecular Structure (SiRMS). The dataset used in our study included 10973 compounds with experimental values of lipophilicity (LogKow ) for different chemical compounds. Random Forest (RF) method was used for statistical modeling at the 2D level of representation of molecular structure. Developed models are adequate and successfully validated with external test sets. Proposed models have clear interpretation due to the use of simplex representation of molecular structure and predict the LogKow values with the accuracy of the best modern models. Thus QSPR models proposed in this study represent powerful and easy-to use virtual screening tool that can be recommended for prediction of octanol-water partition coefficient.

Per aspera ad astra: application of Simplex QSAR approach in antiviral research.

This review explores the application of the Simplex representation of molecular structure (SiRMS) QSAR approach in antiviral research. We provide an introduction to and description of SiRMS, its application in antiviral research and future directions of development of the Simplex approach and the whole QSAR field. In the Simplex approach every molecule is represented as a system of different simplexes (tetratomic fragments with fixed composition, structure, chirality and symmetry). The main advantages of SiRMS are consideration of the different physical-chemical properties of atoms, high adequacy and good interpretability of models obtained and clear procedures for molecular design. The reliability of developed QSAR models as predictive virtual screening tools and their ability to serve as the basis of directed drug design was validated by subsequent synthetic and biological experiments. The SiRMS approach is realized as the complex of the computer program 'HiT QSAR', which is available on request.

Hierarchic system of QSAR models (1D-4D) on the base of simplex representation of molecular structure.

In this work, a hierarchic system of QSAR models from 1D to 4D is considered on the basis of the simplex representation of molecular structure (SiRMS). The essence of this system is that the QSAR problem is solved sequentially in a series of the improved models of the description of molecular structure. Thus, at each subsequent stage of a hierarchic system, the QSAR problem is not solved ab ovo, but rather the information obtained from the previous step is used. Actually, we deal with a system of solutions defined more exactly. In the SiRMS approach, a molecule is represented as a system of different simplex descriptors (tetratomic fragments with fixed composition, structure, chirality and symmetry). The level of simplex-descriptor detail increases consecutively from 1D to 4D representations of molecular structure. It enables us to determine the fragments of structure that promote or interfere with the given biological activity easily. Molecular design of compounds with a given level of activity is possible on the basis of SiRMS. The efficiency of the method is demonstrated for the example of the analysis of substituted piperazines affinity for the 5-HT1A receptor.