Article
Multidisciplinary Sciences
Mihaly Badonyi, Joseph A. Marsh
Summary: Protein complex assembly during translation may counteract the dominant-negative effect and is less associated with autosomal dominant disorders and dominant-negative disease mutations. Complexes with known dominant-negative effects tend to expose their interfaces late during translation, reducing the likelihood of cotranslational assembly. A computational model combining complex properties and other features can predict proteins associated with non-loss-of-function disease mechanisms.
Article
Physics, Fluids & Plasmas
W. Tarnowski, I. Yusipov, T. Laptyeva, S. Denisov, D. Chruscinski, K. Zyczkowski
Summary: By studying ensembles of quantum and classical random generators of N-dimensional Markovian evolution, we demonstrate the relationship between the two types of generators through superdecoherence. Increasing the strength of superdecoherence gradually leads to a sharp quantum-to-classical transition. Additionally, microscopic correlation between neighboring eigenvalues and the presence of horseshoe distribution, emblematic of the Ginibre universality class, is observed in both types of random generators even under superdecoherence and supercoherification.
Article
Multidisciplinary Sciences
Christoffer Norn, Basile I. M. Wicky, David Juergens, Sirui Liu, David Kim, Doug Tischer, Brian Koepnick, Ivan Anishchenko, Foldit Players, David Baker, Sergey Ovchinnikov
Summary: The protein design problem aims to find an appropriate amino acid sequence for a desired protein structure, with optimization over all possible sequences and structures using protein structure prediction and backpropagation. The trRosetta model is more effective than Rosetta single-point energy estimations, and combining trRosetta and Rosetta models can result in more funneled energy landscapes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Physics, Fluids & Plasmas
Roman Riser, Peng Tian, Eugene Kanzieper
Summary: This paper introduces a method of autocovariance in the early days of random matrix theory to investigate the correlations between individual eigenlevels. By establishing a link between autocovariance and power spectrum, the researchers find that for symmetry index 2, the power spectrum can be represented by a fifth Painleve transcendent. High-precision numerical simulations provide independent support to this result.
Article
Physics, Fluids & Plasmas
K. Hagino, G. F. Bertsch
Summary: The Gaussian orthogonal ensemble (GOE) is used to describe phenomena in strongly coupled quantum systems and explain fluctuations in decay rates. Coupling to decay channels can change the effective number of degrees of freedom. The effective number of degrees of freedom depends on the control parameter rho F, and can be analytically derived through the model.
Review
Biochemical Research Methods
Wenze Ding, Kenta Nakai, Haipeng Gong
Summary: This review explores the recent advances in deep learning-based protein design methods and compares them with conventional knowledge-based approaches through notable cases. The development of deep learning in structure-based and sequence-based protein design is described, as well as the applications of deep reinforcement learning in protein design. Future perspectives on design goals, challenges, and opportunities are thoroughly discussed.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Multidisciplinary Sciences
J. Dauparas, I. Anishchenko, N. Bennett, H. Bai, R. J. Ragotte, L. F. Milles, B. I. M. Wicky, A. Courbet, R. J. de Haas, N. Bethel, P. J. Y. Leung, T. F. Huddy, S. Pellock, D. Tischer, F. Chan, B. Koepnick, H. Nguyen, A. Kang, B. Sankaran, A. K. Bera, N. P. King, D. Baker
Summary: This article introduces a deep learning-based protein sequence design method, ProteinMPNN, which has shown outstanding performance in both theoretical and experimental tests, suggesting its wide applicability.
Article
Statistics & Probability
Timothy W. Waite, David C. Woods
Summary: In game theory and statistical decision theory, random decision strategies often outperform deterministic strategies in minimizing expected loss. Novel and flexible random design strategies are shown to have better properties than deterministic counterparts in linear model estimation and prediction, with stronger bounds on the loss distribution. The use of random strategies in experimental design selection can lead to finite bounds on expected loss, compared to existing deterministic designs where expected loss is unbounded.
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
(2022)
Article
Physics, Multidisciplinary
Thomas Guhr, Andreas Schell
Summary: The study focuses on a doubly correlated algebraic model for real covariance or correlation matrices, known as the matrix variate t-distribution. It explores matrix moments, specifically calculating the first and second moments, with the computation of the latter being non-trivial. The problem is solved by relating it to the Aomoto integral and extending the recursive technique to calculate Ingham-Siegel integrals, with results compared to the Gaussian case.
JOURNAL OF PHYSICS A-MATHEMATICAL AND THEORETICAL
(2021)
Article
Cell Biology
Yuhua Fu, Ningxie Chen, Ziying Wang, Shouqing Luo, Yu Ding, Boxun Lu
Summary: This study demonstrates a novel strategy to degrade non-protein biomolecules using autophagy-tethering compounds targeting lipid droplets. By designing compounds that interact with both lipid droplets and the key autophagosome protein LC3, researchers were able to effectively clear lipid droplets and rescue related phenotypes in cells and mouse models. The mechanism of action was confirmed to be mediated through LC3 and autophagic degradation. This proof-of-concept study suggests the potential application of this strategy to other protein and non-protein targets.
Article
Biochemical Research Methods
Leonardo Castorina, Rokas Petrenas, Kartic Subr, Christopher W. Wood
Summary: With the increasing amount of protein structure data and advances in machine learning, the number of available protein sequence design methods is rapidly expanding. To effectively utilize a design method, understanding its performance nuances and how it varies by design target is crucial. PDBench is introduced as a collection of proteins and standard tests to assess the performance of sequence design methods. Compared to previous benchmarking sets, PDBench aims to maximize the structural diversity of the benchmark to provide valuable biological insights into the behavior of sequence design methods, which is essential for evaluating their performance and practical utility. We believe these tools are valuable for guiding the development of novel sequence design algorithms and assisting users in choosing a method that best suits their design target.
Article
Chemistry, Multidisciplinary
Jin Yan, Xiaoqiang Zheng, Weiming You, Wangxiao He, Guang-Kui Xu
Summary: This study introduces a new method to calculate the affinity of PPI modulators and significantly increases the affinity of PPI modulators through a simple homodimerization strategy.
Article
Mechanics
Antoine Maillard, Florent Krzakala, Marc Mezard, Lenka Zdeborova
Summary: The paper discusses matrix factorization and extensive-rank matrix denoising problems using high-temperature expansions to find more accurate solutions. It provides a systematic approach to derive corrections to existing approximations, taking into account the specific structure of correlations in the problems.
JOURNAL OF STATISTICAL MECHANICS-THEORY AND EXPERIMENT
(2022)
Article
Biochemistry & Molecular Biology
Jian Chang, Chengxin Zhang, Huaqiang Cheng, Yan-Wen Tan
Summary: Protein engineering using rational design by bioinformatics can enhance thermostability of proteins without time-consuming experimental screenings. Utilizing a primary-sequence-based algorithm can help identify amino acid sites related to thermostability, leading to the construction of mutants with improved enzymatic activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physics, Multidisciplinary
Sergei Kozyrev
Summary: A learning model is introduced as a generalization of Eigen's quasispecies model in population genetics. The error catastrophe in Eigen's model is discussed as the divergence of the Perron-Frobenius eigenvalue of the Riccati model in the limit of large matrices. The analogy between the error catastrophe and overfitting in learning theory is proposed, providing a criterion for detecting overfitting.
Article
Chemistry, Medicinal
Leena Aggarwal, Parbati Biswas
Summary: The hydration thermodynamics of Aβ and its FAD mutants were investigated using MD simulations and 3D-RISM theory, revealing that mutations affect hydration free energy through electrostatic and nonelectrostatic contributions, resulting in different aggregation propensities and early onset Alzheimer's disease risk.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
Leena Aggarwal, Parbati Biswas
Summary: This study investigates the hydration thermodynamics of different mutants of alpha-synuclein related to familial Parkinson's disease using a computational approach. The results show that the hydration free energy and interaction volume play a crucial role in determining the aggregation kinetics of alpha-synuclein upon mutation.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Physical
Shivangi Sharma, Vishal Singh, Parbati Biswas
Summary: The effect of ligand binding on the conformational transitions of the add A-riboswitch in cellular environments is theoretically investigated. It was found that the transition path time for the riboswitch aptamer is longer when the ligand is bound compared to when it is unbound. Additionally, the transition path time decreases with an increase in the barrier height, which may seem counterintuitive.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Mechanics
Manisha Handa, Parbati Biswas
Summary: This study theoretically investigates the intramolecular relaxation dynamics of unconcatenated ring polymers in dilute solutions, finding that excluded volume interactions can decrease relaxation rates and expand the width of the relaxation spectrum.
JOURNAL OF RHEOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Vishal Singh, Parbati Biswas
Summary: The dynamics of conformational transitions of the disordered protein, amyloid-beta, were studied through simulations, revealing a two-state transition in the energy landscape. The variation of the transmission coefficient also indicated the breakdown of Kramers and Grote-Hynes theories and the emergence of dynamic disorder. These findings provide insight into the unfold-misfold transition dynamics of amyloid-beta.
Article
Polymer Science
Manisha Handa, Parbati Biswas
Summary: This study investigates the relaxation dynamics of ring polymers in dilute solutions with both repulsive excluded volume interactions and attractive interactions using Rouse-Zimm theory. The results show that the overall motion dominates the relaxation of ring polymers with repulsive interactions, while the opposite is true for ring polymers with attractive interactions. The spin-lattice relaxation rate exhibits a characteristic maximum at different frequencies.
Article
Biology
Sujeet Kumar Mishra, Kunhe Li, Simon Brauburger, Arnab Bhattacherjee, Nestor Norio Oiwa, Dieter W. Heermann
Summary: Nucleosome positioning plays a crucial role in important biological processes and can be used to predict genome function and chromatin organization. This study developed a theoretical model to analyze nucleosome positioning data and obtained genome-wide clustering in Candida albicans. The clustering revealed different nucleosome distributions and gene densities that govern differential gene expression patterns. Furthermore, these distribution patterns were conserved throughout the genome and within species.
Article
Biophysics
Anupam Mondal, Sujeet Kumar Mishra, Arnab Bhattacherjee
Summary: This study reveals the mechanism of interaction between transcription factors and nucleosomes. The research shows that the transcription factors cluster bind to the entry-exit region of nucleosomes and regulate gene search and regulation by altering nucleosome dynamics and entropy.
BIOPHYSICAL JOURNAL
(2022)
Article
Chemistry, Physical
Sujeet Kumar Mishra, Arnab Bhattacherjee
Summary: By developing a theoretical model based on a stochastic approach, the researchers investigated the target search mechanism of multiple Transcription Factors (TFs) on nucleosomal DNA. They analyzed when the TFs hierarchically search their binding motifs and when they simultaneously proceed via the formation of a protein-protein complex.
Article
Chemistry, Multidisciplinary
Priya Dey, Parbati Biswas
Summary: The hydration thermodynamics of various protein structures, including globular protein, intrinsically disordered protein regions, and fully disordered protein, was studied using molecular dynamics simulations and 3D-RISM theory. The hydration free energy was found to decrease with an increase in percentage disorder, indicating favorable interactions between disordered proteins and solvent. The contribution of electrostatic interactions and percentage disorder to the aggregation propensity of proteins was confirmed. Residue-wise decomposition analysis showed that disordered regions play a bigger role in hydration free energy. The dominant contribution of electrostatic interactions was observed, with negatively charged residues contributing more to proteins with negative net charge and positively charged residues contributing more to proteins with positive net charge.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Arnab Bhattacherjee
Summary: Human Replication Protein A (hRPA) is a multidomain protein that interacts with ssDNA intermediates, providing stability during DNA metabolism. The binding mechanism between hRPA and ssDNA was studied using a computational framework, revealing two distinct binding mechanisms based on the flexibility of hRPA domains. The results provide new insights into the dynamics of hRPA binding to ssDNA and pave the way for investigating the details of ssDNA-protein interactions.
Article
Chemistry, Physical
Sujeet Kumar Mishra, Arnab Bhattacherjee
Summary: Almost 75% of eukaryotic DNA is occupied by nucleosomes, which consist of histone proteins and DNA. Nucleosome dynamics regulate the accessibility of DNA sites for nonhistone proteins, therefore controlling the processes involved in determining cell identity and fate. This study proposes an analytical framework to analyze the impact of nucleosome dynamics on the target search process of transcription factors.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Chemistry, Physical
Sumit Kumar, Parbati Biswas
Summary: Ring polymers differ significantly from linear polymers in terms of their properties such as intrinsic viscosity, complex viscosity, and dielectric relaxation. Excluded volume interactions and hydrodynamic interactions play important roles in ring polymers. In addition, the size of the ring and the interactions between rings also have an impact on the properties of ring polymers.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Shivangi Sharma, Vishal Singh, Parbati Biswas
Summary: In this study, the conformational transitions of the adenosine deaminase Ariboswitch aptamer were investigated using steered molecular dynamics (SMD) simulations and the generalized Langevin equation. The results showed that the unfold-fold transitions are faster and more probable than the fold-unfold transitions, and the transition path time is insensitive to the exact mechanism of the transition events. The complexity of the cellular environment increases the mean first passage time.
ACS PHYSICAL CHEMISTRY AU
(2022)
Article
Biochemistry & Molecular Biology
Anupam Mondal, Sangeeta, Arnab Bhattacherjee
Summary: By developing a computational framework, researchers have discovered the impact of DNA supercoiling on gene transcription regulation and revealed the mechanism behind the differential diffusion behavior of proteins on different supercoiled DNA. These findings significantly advance the understanding of the function and organization of chromatin inside cells.
NUCLEIC ACIDS RESEARCH
(2022)
