Article
Chemistry, Medicinal
Maohua Yang, Yegen Tang, Jingwei Weng, Zhijun Liu, Wenning Wang
Summary: The D-glucose/D-galactose-binding protein (GGBP) from Escherichia coli is a substrate-binding protein (SBP) associated with sugar transport and chemotaxis. It is also a calcium-binding protein, and the study found that calcium binding can stabilize the open conformation of GGBP, playing an active regulatory role in tuning the conformational distribution of the protein.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Physical
Anupam Anand Ojha, Saumya Thakur, Surl-Hee Ahn, Rommie E. Amaro
Summary: Recent advances in computational power and algorithms have extended the time scales of molecular dynamics (MD) simulations. However, MD simulations still face limitations in observing conformational transitions associated with biomolecular processes. To address this challenge, enhanced sampling techniques such as the weighted ensemble (WE) method have been developed to estimate kinetic rate constants by sampling transitions between metastable states using weighted trajectories. In this study, deep-learned kinetic modeling approaches are introduced to extract statistically relevant information from short MD trajectories and provide a well-sampled initial state distribution for WE simulations. This hybrid approach overcomes statistical bias and produces a refined free energy landscape closer to the steady state, enabling efficient sampling of kinetic properties.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Biochemical Research Methods
Hovakim Grabski, Siranuysh Ginosyan, Susanna Tiratsuyan
Summary: Enteropathogenic Escherichia coli is a significant pathogen causing persistent diarrhea in children worldwide. The bacteria can form biofilms, and its mechanisms, including virulence factors and biofilm formation, are regulated by quorum sensing. SdiA receptor in enteropathogenic E. coli can detect autoinducers and may serve as a potential target for anti-infectious techniques.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Materials Science, Multidisciplinary
Bojun Liu, Yunrui Qiu, Eshani C. Goonetilleke, Xuhui Huang
Summary: Self-assembly is a powerful approach for fabricating advanced materials, but understanding its kinetics at a molecular level is challenging. Kinetic network models based on molecular dynamics simulations have shown potential in elucidating self-assembly pathways. This article discusses challenges in using these models and reviews the recent development of machine learning approaches to address them. It also highlights the potential of these models in molecular self-assembly studies and material design.
Article
Chemistry, Physical
Siqin Cao, Yunrui Qiu, Michael L. Kalin, Xuhui Huang
Summary: The generalized master equation (GME) is a powerful method for studying biomolecular dynamics. We present a new method, the Integrative GME (IGME), which analytically solves the GME when the memory kernels have decayed to zero, overcoming the challenges of the quasi Markov State Model (qMSM).
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Xiaowei Wang, Tiantian Xu, Yuan Yao, Peter Pak-Hang Cheung, Xin Gao, Lu Zhang
Summary: This study utilizes molecular dynamics simulations to construct a Markov state model and investigate the translocation dynamics of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). The research reveals the key steps of translocation and the asynchronous movement of the template-primer duplex, providing new insights into viral replication and transcription.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Kalyan S. Chakrabarti, Simon Olsson, Supriya Pratihar, Karin Giller, Kerstin Overkamp, Ko On Lee, Vytautas Gapsys, Kyoung-Seok Ryu, Bert L. de Groot, Frank Noe, Stefan Becker, Donghan Lee, Thomas R. Weikl, Christian Griesinger
Summary: The study presents a theoretical and experimental framework to investigate protein binding mechanisms on sub-millisecond timescales. Using nuclear magnetic resonance and molecular dynamics simulations, the authors find that the binding mechanism between ubiquitin and the SH3 domain is based on conformational selection.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Ruidan Shen, Rory M. Crean, Keith J. Olsen, Marina Corbella, Ana R. Calixto, Teisha Richan, Tiago A. S. Brandao, Ryan D. Berry, Alex Tolman, J. Patrick Loria, Sean J. Johnson, Shina C. L. Kamerlin, Alvan C. Hengge
Summary: In this study, a chimeric protein was constructed and analyzed biochemically, structurally, and dynamically to reveal the important role of the conserved WPD-loop in protein tyrosine phosphatases. The stability and activity of the chimeric protein were influenced by loop conformational dynamics and non-catalytic residues.
Article
Biology
Lizhe Zhu, Hanlun Jiang, Siqin Cao, Ilona Christy Unarta, Xin Gao, Xuhui Huang
Summary: The study utilized extensive molecular dynamics simulations to build a quasi Markov State Model, revealing the dynamics of mRNA recognition by Argonaute. Motion modes dependent on the coordination of target phosphate groups and the role of Helix-7 in reducing target mRNA volume accessibility and facilitating base-pair formation were discovered through simulations. The study also demonstrated the potential of qMSM in investigating complex conformational changes in biomolecular systems.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Emilia P. Barros, Ozlem Demir, Jenaro Soto, Melanie J. Cocco, Rommie E. Amaro
Summary: The study demonstrates the potential significance of mutated p53 in cancer therapy by reactivating it. The mutations induce conformational changes in the important loops L6 and L1 of the p53 protein, suggesting potential new therapeutic targets.
Review
Chemistry, Multidisciplinary
Aldo Glielmo, Brooke E. Husic, Alex Rodriguez, Cecilia Clementi, Frank Noe, Alessandro Laio
Summary: This review provides a comprehensive overview of the importance of unsupervised learning in analyzing data from atomistic and molecular simulations, discussing state-of-the-art algorithms and methods in feature representation, dimensionality reduction, density estimation, clustering, and kinetic models. The article is well-structured, with detailed discussions in each section on the mathematical and algorithmic foundations, strengths and limitations of each method, and specific applications in analyzing molecular simulation data.
Article
Biochemistry & Molecular Biology
Mueed Ur Rahman, Kaiyuan Song, Lin-Tai Da, Hai-Feng Chen
Summary: By using molecular dynamics simulations and Markov state model, the early oligomerization mechanism of A beta(16-22) peptides was investigated. It was found that the dimeric form of the peptides adopted globular random-coil or extended beta-strand like conformations, and intermolecular antiparallel beta-sheets were the most common type of secondary structure in the observed dimers. The states containing beta secondary structure and extended coiled structures were majorly involved in aggregation.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Water Resources
Nicholas B. Engdahl, Tomas Aquino
Summary: Correlated velocity models have proved useful in describing solute transport behaviors in porous media. This study extends the application of spatial Markov models to time-varying flows and proposes alternative numerical implementations. The validity and efficiency of the models are determined based on standard physical quantities, and clear tests are provided for the applicability of transient, upscaled models.
ADVANCES IN WATER RESOURCES
(2022)
Article
Biochemical Research Methods
R. C. N. Quiroz, E. A. Philot, I. J. General, D. Perahia, A. L. Scott
Summary: This study investigates the conformational dynamics and stability of hDAT states under different phosphorylation sites. The results show that phosphorylation conditions affect the rate of dopamine transport and support the hypothesis of decreased transport rate in the NP-333 system. Single phosphorylation or dephosphorylation can alter protein motions and affect the stability and transition of states involved in dopamine transport.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2023)
Article
Neurosciences
Takahiro Ezaki, Yu Himeno, Takamitsu Watanabe, Naoki Masuda
Summary: Recent studies have suggested that summarizing brain activity into hidden states dynamics is a promising tool for understanding brain function. Hidden Markov models (HMMs) are commonly used to infer neural dynamics, but the impact of assuming Markovian structure in neural time series data needs further examination. Comparisons between GMM and HMM show that HMM generally provides better accuracy in estimating hidden states, but GMM can be a viable alternative under certain conditions like low sampling frequency or short data length.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Md Shafiqul Islam, Samuel L. Junod, Si Zhang, Zakey Yusuf Buuh, Yifu Guan, Mi Zhao, Kishan H. Kaneria, Parmila Kafley, Carson Cohen, Robert Maloney, Zhigang Lyu, Vincent A. Voelz, Weidong Yang, Rongsheng E. Wang
Summary: The authors report a peptide macrocyclization and stapling strategy based on a fluorine thiol displacement reaction, which enables selective modification of unprotected peptides, resulting in improved stability, affinity, cellular uptake, and inhibition of cancer cells.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Weiyi Qian, Jian-Xia Xue, Jinxin Xu, Feng Li, Guang-Feng Zhou, Fang Wang, Rong-Hua Luo, Jinsong Liu, Yong-Tang Zheng, Guo-Chun Zhou
Summary: This study focused on the design, synthesis, and evaluation of compounds based on indoline structural skeleton against DENV infection. 13 active compounds against DENV infection were discovered, and their structure-activity relationship (SAR) was summarized. Compound 15 targets the post-entry stages of DENV2 viral life cycle.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Yunhui Ge, Vincent A. Voelz
Summary: Accurate and efficient simulation of protein-ligand interactions is crucial for computational drug discovery. In this study, we compared the performance of two Multiensemble Markov Model approaches for estimating ligand binding affinities and rates and found that the transition-based reweighting analysis method (TRAM) outperformed the Maximum Caliber (MaxCal) based method. Subsampling of trajectories improved the accuracy of both methods.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Dylan Novack, Lei Qian, Gwyneth Acker, Vincent A. Voelz, Richard H. G. Baxter
Summary: Specific mutations in the forkhead domain of FOXO1 are found to be associated with loss of function in diffuse large B-cell lymphoma. Experimental and computational studies reveal that these mutations disrupt the stability of the FOX domain, and simulations with atomic detail are important for accurate prediction of mutational effects on folding stability.
Article
Chemistry, Multidisciplinary
Guang-Feng Zhou, Cong-Qiang Xie, Jian-Xia Xue, Jing-Bo Wang, Yu-Zhuo Yang, Chang-Bo Zheng, Rong-Hua Luo, Ren-Hua Yang, Wen Chen, Liu-Meng Yang, Yue-Ping Wang, Hong-Bin Zhang, Yan-Ping He, Yong-Tang Zheng
Summary: In this study, acetylarylamine-S-DACOs derivatives were found to have inhibitory activity against Zika virus, with compound 4w showing the best anti-ZIKV activity by targeting the ZIKV NS5 RNA-dependent RNA polymerase (RdRp). These promising results provide a future prospective for the development of ZIKV RdRp inhibitors.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Victoria J. Laye, Shahlo Solieva, Vincent A. Voelz, Shiladitya DasSarma
Summary: In this study, the polyextremophilic activity of the beta-galactosidase enzyme in the haloarchaeon Halorubrum lacusprofundi was investigated. The results showed that the catalytic efficiency of the enzyme improved with increasing temperature and salinity, while the substrate binding capacity decreased with decreasing temperatures and increasing salinity. Molecular dynamics simulations revealed that the enzyme's flexibility played a crucial role in its function, and regions distant from the active site were found to be important in adapting to extreme conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Guang-Feng Zhou, Weiyi Qian, Feng Li, Ren-Hua Yang, Na Wang, Chang-Bo Zheng, Chun-Yan Li, Xue-Rong Gu, Liu-Meng Yang, Jinsong Liu, Si-Dong Xiong, Guo-Chun Zhou, Yong-Tang Zheng
Summary: A compound called ZFD-10 has been found to exhibit anti-ZIKV activity and effectively protect mice from ZIKV infection. ZFD-10 targets the viral replication enzyme, inhibiting the infection. This discovery holds significant implications for the prevention and treatment of ZIKV.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Robert M. Raddi, Yunhui Ge, Vincent A. Voelz
Summary: Bayesian Inference of Conformational Populations (BICePs) version 2.0 is a Python package that reweights theoretical predictions using experimental measurements. It supports various NMR observables and provides automatic analysis of the posterior distribution. It is a powerful and user-friendly software with improvements from the previous version.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Virology
Guang-Feng Zhou, Feng Li, Jian-Xia Xue, Weiyi Qian, Xue-Rong Gu, Chang-Bo Zheng, Chunyan Li, Liu-Meng Yang, Si-Dong Xiong, Guo-Chun Zhou, Yong-Tang Zheng
Summary: This study focuses on the anti-ZIKV effects of fused tricyclic derivatives and finds that they have potential as drug leads. Some compounds are broad-spectrum inhibitors of both ZIKV and DENV, while others selectively inhibit one of the viruses. Certain compounds are more active against Asian ZIKV strains and silylation enhances their antiviral activity. The study also highlights the importance of structural features in compound efficacy.
Article
Multidisciplinary Sciences
Andrew Muenks, Samantha Zepeda, Guangfeng Zhou, David Veesler, Frank DiMaio
Summary: As cryo-EM becomes commonplace in drug discovery, tools for automating small molecule structure determination are needed. Here, the authors present a map-guided ligand modeling approach that can build ligand structures at resolutions common in cryo-EM. This method can accurately predict the positions of ligands and surrounding side chains in maps with local resolutions as low as 4.5 angstroms.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Robert M. Raddi, Yunhui Ge, Vincent A. Voelz
Summary: Bayesian Inference of Conformational Populations (BICePs) version 2.0 is a free, open-source Python package that reweights theoretical predictions of conformational states using experimental measurements. The latest version of BICePs (v2.0) supports various experimental NMR observables and provides convenient data preparation and processing. It also allows for automatic analysis of sampled posterior and provides coding examples for reference.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Matthew F. D. Hurley, Robert M. Raddi, Jason G. Pattis, Vincent A. Voelz
Summary: This study implemented an expanded ensemble workflow and distributed computing to predict binding free energies between small molecules and pillar[6]arene. The results suggest that the expanded ensemble method can efficiently predict and rank absolute binding free energies.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Meeting Abstract
Biophysics
Thi Dung Nguyen, Robert Raddi, Mate Erdelyi, Vincent Voelz
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Dylan Novack, Paula Garavito, Frank D. Teets, Christopher D. Bahl, Vincent Voelz
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Si Zhang, Vincent A. Voelz
BIOPHYSICAL JOURNAL
(2022)