High-precision energy ranking method for crystal structure prediction of organic molecules

Abstract

The invention belongs to the technical field of organic molecular crystal structure, and specifically relates to a high-precision energy ranking method used in the prediction of organic molecular crystal structure, including determining the quantum mechanical action radius of the central unit cell; in the central unit cell, the density block interaction algorithm is used to carry out Energy calculation; within the range of radius R, the effect of molecules outside the central unit cell on the molecules in the central unit cell can be calculated under the precision of quantum mechanics; under the condition of classical molecular mechanics precision, outside the range of calculation radius R, the periodically extended unit The action energy of the cell on the molecules in the central unit cell; calculate the total energy of the crystal, which includes the energy in the central unit cell and the energy between the central unit cell and the periodically extended unit cell. The invention improves the energy calculation efficiency in the drug molecular crystal, and the precise energy feedback will guide the CSP to find the real low-energy dominant crystal form in the correct direction during the crystal prediction process.

Description

Technical field [0001] The present invention belongs to the technical field of organic molecular crystal structures, and more particularly to high precision energy ranking methods for organic molecular crystal structural prediction. Background technique [0002] The compound having a different crystal structure is referred to as a polymorphic phenomenon. The key physicochemical properties of the compound itself such as density, morphology, solubility, solubility, etc. are strongly affected by its crystal form. For pharmaceuticals, the crystal form can strongly affect the bioavailability of the drug, and ultimately affect the treatment of the drug. Experimental polymorphic drug screening has become an essential part of standard drug research and development. In the experiment, people manually or manually set key crystallization parameters, but the correct crystallization conditions are difficult to obtain in a short period of time. An alternative solution is to perform crystal str...

AI Technical Summary

Problems solved by technology

There are currently two main challenges in this field, one is the completeness of the crystal space sampling, and the other is the accuracy of the energy ranking of the crystal structure

The first challenge has been greatly improved, but the second point, the precise energy arrangement of the structure is still the bottleneck restricting the large-scale application of CSP in the pharmaceutical industry

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