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Molecular Crystal Polymorph Prediction: High Accuracy at Lower Computational Cost

分子晶体多晶型预测：以较低的计算成本实现高精度

基本信息

批准号：
1955554
负责人：
Gregory Beran
金额：
$ 49.92万
依托单位：
University of California-Riverside
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1955554&HistoricalAwards=false
关键词：
Molecular Crystal Polymorph Prediction Accuracy

项目摘要

Professor Gregory Beran of the University of California-Riverside is supported by an award from the Chemical Theory, Models and Computational Methods program in the Chemistry Division to develop new computational tools that will facilitate the prediction of three-dimensional crystal structures. Knowledge of molecular crystal structures is essential in pharmaceuticals and many other areas of chemistry. Different crystal packing arrangements, or “polymorphs,” of the same molecule can exhibit vastly different properties. The occurrences of undesirable polymorphs have caused major drug recalls and other serious problems for patients and pharmaceutical manufacturers in the past. The pharmaceutical industry increasingly employs crystal structure prediction to complement their experimental drug formulation efforts and to reduce the potential for polymorphism-related problems. It has recently been discovered that the current theoretical models in widespread use exhibit significant problems for predicting the crystal structures of drug molecules. This project is developing new computational models that correct these weaknesses and improve the reliability with which crystal structures can be predicted. Software developed by this project will be released to the community as free, open-sourcesoftware. Beyond the core research, Professor Beran is actively involved in pedagogical efforts to help train next-generation scientists, a large proportion of whom come from low-income, first-generation, and/or traditionally underrepresented minority demographics. This research occurs in three parts. First, new computationally-practical electronic structure methods for modeling the non-covalent interactions that govern molecular conformation and crystal packing are being developed to enable identification of good initial crystal structures. Second, an approach that combines the strengths of the new electronic structure methods for describing intramolecular interactions with the lower computational costs of density functional theory for modeling intermolecular interactions is being developed to enable improved crystal structure predictions in pharmaceutical compounds. Finally, new lower-cost approximations for handling the vibrational contributions to crystalline stability are being investigated to allow investigation of how temperature affects polymorph stability. This project is developing new computational models that correct weaknesses in current theoretical models and improve the reliability with which crystal structures can be predicted. Software developed by this project will be released to the community as free, open-source software.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

加州大学河滨分校的Gregory Beran教授获得了化学系化学理论，模型和计算方法项目的奖励，以开发新的计算工具，促进三维晶体结构的预测。分子晶体结构的知识在制药和许多其他化学领域是必不可少的。相同分子的不同晶体堆积排列或“多晶型物”可以表现出截然不同的性质。在过去，不良多晶型物的出现已经引起了患者和制药商的重大药物召回和其他严重问题。制药行业越来越多地采用晶体结构预测来补充他们的实验药物配方的努力，并减少潜在的多晶型相关的问题。最近发现，目前广泛使用的理论模型在预测药物分子的晶体结构方面存在显著的问题。该项目正在开发新的计算模型，以纠正这些弱点，提高预测晶体结构的可靠性。该项目开发的软件将作为免费的开源软件向社区发布。在核心研究之外，Beran教授积极参与教学工作，以帮助培养下一代科学家，其中很大一部分来自低收入，第一代和/或传统上代表性不足的少数民族人口。本研究分为三个部分。首先，正在开发新的计算实用的电子结构方法，用于对支配分子构象和晶体堆积的非共价相互作用进行建模，以识别良好的初始晶体结构。第二，正在开发一种方法，该方法结合了新的电子结构方法的优势，用于描述分子内相互作用，具有较低的计算成本的密度泛函理论用于建模分子间相互作用，以提高药物化合物的晶体结构预测。最后，新的低成本近似处理的振动贡献结晶稳定性正在调查，以允许调查温度如何影响多晶型物的稳定性。该项目正在开发新的计算模型，以纠正当前理论模型的弱点，并提高预测晶体结构的可靠性。该项目开发的软件将作为免费的开源软件向社区发布。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effect of Fluorination on the Polymorphism and Photomechanical Properties of Cinnamalmalononitrile Crystals

DOI：
10.1021/acs.cgd.2c00930
发表时间：
2022-11
期刊：
Crystal Growth & Design
影响因子：
0
作者：
T. J. Gately;C. Cook;Raghad Almuzarie;I. Islam;Zachary S. Gardner;R. Iuliucci;R. Al‐Kaysi;G. Beran;C. Bardeen
通讯作者：
T. J. Gately;C. Cook;Raghad Almuzarie;I. Islam;Zachary S. Gardner;R. Iuliucci;R. Al‐Kaysi;G. Beran;C. Bardeen

The interplay of intra- and intermolecular errors in modeling conformational polymorphs

DOI：
10.1063/5.0088027
发表时间：
2022-03-14
期刊：
JOURNAL OF CHEMICAL PHYSICS
影响因子：
4.4
作者：
Beran, Gregory J. O.;Wright, Sarah E.;Cruz-Cabeza, Aurora J.
通讯作者：
Cruz-Cabeza, Aurora J.

Correcting π-delocalisation errors in conformational energies using density-corrected DFT, with application to crystal polymorphs

使用密度校正 DFT 校正构象能中的 α 离域误差，并应用于晶体多晶型物

DOI：
10.1080/00268976.2022.2138789
发表时间：
2023
期刊：
Molecular Physics
影响因子：
1.7
作者：
Rana, Bhaskar;Beran, Gregory J.;Herbert, John M.
通讯作者：
Herbert, John M.

Reduced-cost supercell approach for computing accurate phonon density of states in organic crystals

DOI：
10.1063/5.0032649
发表时间：
2020-12-14
期刊：
JOURNAL OF CHEMICAL PHYSICS
影响因子：
4.4
作者：
Cook, Cameron;Beran, Gregory J. O.
通讯作者：
Beran, Gregory J. O.

Effect of halogen substitution on energies and dynamics of reversible photomechanical crystals based on 9-anthracenecarboxylic acid

DOI：
10.1039/d1ce00846c
发表时间：
2021-08
期刊：
CrystEngComm
影响因子：
3.1
作者：
T. J. Gately;W. Sontising;Connor J. Easley;I. Islam;R. Al‐Kaysi;G. Beran;C. Bardeen
通讯作者：
T. J. Gately;W. Sontising;Connor J. Easley;I. Islam;R. Al‐Kaysi;G. Beran;C. Bardeen