Crystal Structure Prediction

Traditionally, crystal polymorph studies rely almost exclusively on experimental screening. However, under the constraints of time and limited supply of raw materials, it is often challenging to determine the best crystal form for drug development or ensure completeness in the landscape of crystal forms.


We offer a combined computational chemistry and AI-powered CSP service that help transform the crystal structure prediction process. Our CSP service is able to identify the most stable crystal forms and provide thermodynamic stability ranking of different structures across a range of temperatures (0K-400K) efficiently. With core technologies including our CSP search algorithm, XForce Field, quantum mechanical calculations and free energy calculations, we are able to predict the relative thermodynamic stabilities of different crystal structures with a high accuracy rate. The following figure outlines the overall CSP workflow.


In addition, by leveraging our integrated technology platform, we are able to deploy cloud computing resources, screen crystal structures, and determine their stabilities with accuracy and efficiency at a faster speed compared to that of traditional methods. Instead of two months as typically required by the traditional experimental methods, we are able to deliver the CSP results for a common-case small molecule within two to three weeks. Our technologies are also applicable to more complex molecular systems, such as highly flexible molecules with more than 15 rotatable bonds, complex molecules with isomerization of multiple flexible rings, as well as multi-component crystals such as salts, co-crystals, hydrates, and solvates.


These CSP results have informed experimental screening efforts and reduced unnecessary experimental trials leading to accelerated selection of the optimal medicinal solid form. This ultimately reduces the risks associated with crystal form selection and increases the success rate of later-stage drug development.

Case Studies

Case Study 1

Selection of Crystal Form



Problem.  A Chinese innovative drug development company intended to determine the optimal crystal form of a drug candidate in its pipeline within two months, in order to control the risk associated with form selection for the clinical studies. Traditional experimental methods could not meet the customer’s strict requirements on the study quality due to the stringent timeline.

Solution.  We conducted a complete solid form risk assessment within 37 days by combining CSP and wet lab experimentation to identify and validate the most ideal crystal form pursuant to the customer’s needs.

Result.  The figure below depicts the timeline and milestones of this project. Our CSP not only identified potential polymorphs, but also guided the experimental screening. Our CSP predicted three potential stable crystal forms within two weeks, which informed the experimental screening to search for one crystal form that might otherwise be missed. The results were eventually validated by wet lab experimentation. Crystal form I was selected as the preferred medicinal form because it is the most thermodynamically stable polymorph, as reflected by its lowest relative free energy at both 0K and 300K.

Case Study 2

Polymorph Risk Assessment

Our CSP service provides complete coverage of crystal structures in the low energy region to ensure the completeness of polymorph screenings. Our results assist pharmaceutical companies in evaluating whether or not there are additional more stable crystal forms that have yet to be crystalized experimentally. Such information facilitates decision-making on the scope of polymorph patent protection and safeguards the drug throughout its exclusivity period.

Problem.  A multinational pharmaceutical company intended to acquire a company that was developing a clinical-stage drug candidate. Through experimental research, the acquiring company found that the to-be-acquired company had not conducted complete crystal form research on the drug candidate. Therefore, there was a potential polymorph patent risk, as well as risk to the bioavailability of the drug through potential polymorph conversion. With the fast approaching negotiation deadline, the to-be-acquired company was not able to conduct sufficient crystal form screenings by traditional experimental methods. The acquiring company sought our assistance to determine the polymorph risk.

Solution.  We conducted CSP calculation in the absence of any experimental information to identify all thermodynamically stable crystal forms.

Result.  Within 17 days, we successfully predicted all three crystal forms and their relative stability. As shown in the following figure, we demonstrated that Form I, which was the crystal form initially selected for clinical trials, was the most stable crystal form. Based on these results, the acquiring company decided to proceed with the acquisition and later marketed the drug candidate according to the original plan.

Case Study 1

Selection of Crystal Form



Problem.  A Chinese innovative drug development company intended to determine the optimal crystal form of a drug candidate in its pipeline within two months, in order to control the risk associated with form selection for the clinical studies. Traditional experimental methods could not meet the customer’s strict requirements on the study quality due to the stringent timeline.


Solution.  We conducted a complete solid form risk assessment within 37 days by combining CSP and wet lab experimentation to identify and validate the most ideal crystal form pursuant to the customer’s needs.


Result.  The figure below depicts the timeline and milestones of this project. Our CSP not only identified potential polymorphs, but also guided the experimental screening. Our CSP predicted three potential stable crystal forms within two weeks, which informed the experimental screening to search for one crystal form that might otherwise be missed. The results were eventually validated by wet lab experimentation. Crystal form I was selected as the preferred medicinal form because it is the most thermodynamically stable polymorph, as reflected by its lowest relative free energy at both 0K and 300K.

Case Study 2

Polymorph Risk Assessment

Our CSP service provides complete coverage of crystal structures in the low energy region to ensure the completeness of polymorph screenings. Our results assist pharmaceutical companies in evaluating whether or not there are additional more stable crystal forms that have yet to be crystalized experimentally. Such information facilitates decision-making on the scope of polymorph patent protection and safeguards the drug throughout its exclusivity period.

Problem.  A multinational pharmaceutical company intended to acquire a company that was developing a clinical-stage drug candidate. Through experimental research, the acquiring company found that the to-be-acquired company had not conducted complete crystal form research on the drug candidate. Therefore, there was a potential polymorph patent risk, as well as risk to the bioavailability of the drug through potential polymorph conversion. With the fast approaching negotiation deadline, the to-be-acquired company was not able to conduct sufficient crystal form screenings by traditional experimental methods. The acquiring company sought our assistance to determine the polymorph risk.


Solution.  We conducted CSP calculation in the absence of any experimental information to identify all thermodynamically stable crystal forms.


Result.  Within 17 days, we successfully predicted all three crystal forms and their relative stability. As shown in the following figure, we demonstrated that Form I, which was the crystal form initially selected for clinical trials, was the most stable crystal form. Based on these results, the acquiring company decided to proceed with the acquisition and later marketed the drug candidate according to the original plan.