High-precision energy ranking method for organic molecular crystal structure prediction

Abstract

The invention belongs to the technical field of organic molecular crystal structures and particularly relates to a high-precision energy ranking method for organic molecular crystal structure prediction. The high-precision energy ranking method comprises the steps of determining a quantum mechanics action radius of a center unit cell; in the center unit cell, carrying out energy calculation by adopting a density block interaction algorithm; within a range of a radius R, calculating action energy of molecules outside the center unit cell on the molecules inside the center unit cell at quantum mechanics precision; calculating the action energy of a periodically extended unit cell on the molecules inside the center unit cell outside the range of the radius R under a classical molecular mechanics precision condition; and calculating total energy of crystal, wherein the total energy of the crystal comprises energy in the center unit cell and the energy between the center unit cell and the periodically extended unit cell. According to the high-precision energy ranking method for organic molecular crystal structure prediction, the energy calculation efficiency and accurate energy feedbackin molecular crystal of a drug are improved, and a CSP is guided to look for a true low-energy dominant crystal form in the right direction in the crystal prediction process.

Description

technical field [0001] The invention belongs to the technical field of organic molecular crystal structures, and in particular relates to a high-precision energy ranking method used in the prediction of organic molecular crystal structures. Background technique [0002] The characteristic of compounds that form different crystal structures is called polymorphism. The key physical and chemical properties of the compound itself, such as density, shape, solubility, dissolution rate, etc., are strongly affected by its crystal form. For pharmaceuticals, the crystal form can strongly affect the bioavailability of the drug and ultimately the therapeutic performance of the drug. Experimental polymorphic drug screening has become an essential part of the standard drug discovery process. In the experiment, people set the key crystallization parameters manually or with the help of robots, but it is difficult to obtain the correct crystallization conditions in a short time through exp...

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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