学术成果

Academic Achievements

期刊：

Journal of Physical Chemistry B

作者：

Muhammad A. Hagras, Michael A. Bellucci, Gianpaolo Gobbo, Ryan A. Marek, and Bernhardt L. Trout*

时间：

2020年10月28日

DOI：

https://pubs.acs.org/doi/abs/10.1021/acs.jpcb.0c07510

Computational Modeling of the Disulfide Cross-Linking Reaction J. Phys. Chem. B 2020, 124, 44, 9840–9851

Disulfide cross-linking is one of the fundamental covalent bonds that exist prevalently in many biological molecules that is involved in versatile functional activities such as antibody stability, viral assembly, and protein folding. Additionally, it is a crucial factor in various industrial applications. Therefore, a fundamental understanding of its reaction mechanism would help gain insight into its different functional activities. Computational simulation of the disulfide cross-linking reaction with hydrogen peroxide (H2O2) was performed at the integrated quantum mechanical/molecular mechanical (QM/MM) level of theory in a water box under periodic boundary conditions. A benchmarking study for the barrier height of the disulfide formation step was performed on a model system between methanethiol and methane sulfenic acid to determine, for the QM system, the best-fit density functional theory (DFT) functional/basis set combination that produces comparable resu ...

期刊：

Chemical Science

作者：

Xue-Xiang Zhang, Huan Qi, Ya-Lan Liu, Song-Qiu Yang, Peng Li, Yan Qiao, Pei-Yu Zhang, Shu-Hao Wen, Hai-long Piao and Ke-Li Han

时间：

2020年9月21日

DOI：

https://pubs.rsc.org/en/content/articlelanding/2020/SC/D0SC04411C#!divAbstract

A fluorophore’s electron-deficiency does matter in designing high-performance near-infrared fluorescent probes

The applications of most fluorescent probes available for Glutathione S-Transferases (GSTs), including NI3 which we developed recently based on 1,8-naphthalimide (NI), are limited by their short emission wavelengths due to insufficient penetration. To realize imaging at a deeper depth, near-infrared (NIR) fluorescent probes are required. Here we report for the first time the designing of NIR fluorescent probes for GSTs by employing the NIR fluorophore HCy which possesses a higher brightness, hydrophilicity and electron-deficiency relative to NI. Intriguingly, with the same receptor unit, the HCy-based probe is always more reactive towards glutathione than the NI-based one, regardless of the specific chemical structure of the receptor unit. This was proved to result from the higher electron-deficiency of HCy instead of its higher hydrophilicity based on a comprehensive analysis. Further, with caging of the autofluorescence being crucial and more difficult to achieve via photoinduced ...

期刊：

Crystal Growth Design

作者：

Mingjun Yang, Eric Dybeck, Guangxu Sun, Chunwang Peng, Brian Samas, Virginia M. Burger, Qun Zeng, Yingdi Jin, Michael A. Bellucci, Yang Liu, Peiyu Zhang, Jian Ma, Yide Alan Jiang, Bruno C. Hancock, Shuhao Wen*, and Geoffrey P. F. Wood

时间：

2020年9月2日

DOI：

https://pubs.acs.org/doi/10.1021/acs.cgd.0c00422

Prediction of the Relative Free Energies of Drug Polymorphs above Zero Kelvin Cryst. Growth Des. 2020, 20, 8, 5211–5224

Crystal structure prediction (CSP) calculations can reduce risk and improve efficiency during drug development. Traditionally, CSP calculations use lattice energies computed through density functional theory. While this approach is often successful in predicting the low energy structures, it neglects the crucial role of thermal effects on polymorph stabilities. In the present study, we develop a robust and efficient protocol for predicting the relative stability of polymorphs at different temperatures. The protocol is executed on a highly parallel cloud computing infrastructure to produce results at time scales useful for drug development timelines. We demonstrate this protocol on molecule XXIII from the sixth crystal structure prediction blind test. Our results predict that Form D is the most stable experimentally observed polymorph at ambient temperature and Form C is the most stable at low temperature consistent with experiments also conducted in the present study. ...

期刊：

Journal of Chemical Information and Modeling

作者：

Junjie Zou, Jian Yin, Lei Fang, Mingjun Yang, Tianyuan Wang, Weikun Wu, Michael A. Bellucci, and Peiyu Zhang*

时间：

2020年7月28日

DOI：

https://pubs.acs.org/doi/10.1021/acs.jcim.0c00679

Computational Prediction of Mutational Effects on SARS-CoV-2 Binding by Relative Free Energy Calculations

The ability of coronaviruses to infect humans is invariably associated with their binding strengths to human receptor proteins. Both SARS-CoV-2, initially named 2019-nCoV, and SARS-CoV were reported to utilize angiotensin-converting enzyme 2 (ACE2) as an entry receptor in human cells. To better understand the interplay between SARS-CoV-2 and ACE2, we performed computational alanine scanning mutagenesis on the “hotspot” residues at protein–protein interfaces using relative free energy calculations. Our data suggest that the mutations in SARS-CoV-2 lead to a greater binding affinity relative to SARS-CoV. In addition, our free energy calculations provide insight into the infectious ability of viruses on a physical basis and also provide useful information for the design of antiviral drugs. ...

期刊：

Organic Process Research & Development

作者：

Yu-hong Lam*, Yuriy Abramov, Ravi S. Ananthula, Jennifer M. Elward, Lori R. Hilden, Sten O. Nilsson Lill, Per-Ola Norrby, Antonio Ramirez, Edward C. Sherer, Jason Mustakis, and Gerald J. Tanoury*

时间：

2020年7月23日

DOI：

https://pubs.acs.org/doi/10.1021/acs.oprd.0c00222

Applications of Quantum Chemistry in Pharmaceutical Process Development: Current State and Opportunities

Application of computational methods to understanding and predicting properties of analogues for drug discovery has enjoyed a long history of success. However, the drug development space (post-candidate selection) is currently experiencing a rapid growth in this arena. Due to the revolution in computing hardware development and improved computational techniques, quantum chemical (QC) calculations have become an essential tool in this space, allowing results from complex calculations to inform chemical development efforts. As a result, numerous pharmaceutical companies are employing QC as part of their drug development workflow. Calculations cover the range of transition state calculations, reaction path determination, and potential energy surface scans, among others. The impact of this rapid growth is realized by providing an in-depth understanding of chemical processes and predictive insight into the outcome of potential process routes and conditions. This review surveys the state ...

期刊：

Crystal Growth Design

作者：

Dr. Yuriy Abramov, Dr. Peiyu Zhang et al.

时间：

2020年01月30日

DOI：

https://pubs.acs.org/doi/10.1021/acs.cgd.9b01153

Computational Insights into Kinetic Hindrance Affecting Crystallization of Stable Forms of Active Pharmaceutical Ingredients

A computational investigation of the potential source of kinetic hindrance for the late appearance of pharmaceutically relevant stable forms of ritonavir, rotigotine, ranitidine hydrochloride, and pharmaceutical compound A was performed along the crystallization coordinates of the relative rates of conformational interconversion, crystal nucleation, and growth. Conformational distribution, classical nucleation, and growth morphology theories were utilized, respectively, to compare the results with those of polymorphic systems, famotidine, nimodipine, paracetamol, indomethacin, tolfenamic acid, and mebendazole for which kinetic hindrance of the stable forms was not reported. The results did not support a potential mechanism of kinetic hindering of the stable polymorphic form due to nucleation and growth limited crystallization. However, a low population of crystallographic conformations of the stable forms in solution allowed us to distinguish the behavior of the late-appearing stabl ...