A5030987631- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Spectroscopy and Quantum Chemical Studies
- Photosynthetic Processes and Mechanisms
- Molecular Junctions and Nanostructures
- Cancer Cells and Metastasis
- Genomics and Chromatin Dynamics
- Photochemistry and Electron Transfer Studies
- Microtubule and mitosis dynamics
- Gene Regulatory Network Analysis
- RNA modifications and cancer
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Bacterial Genetics and Biotechnology
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Evolution and Genetic Dynamics
- DNA and Nucleic Acid Chemistry
- Mass Spectrometry Techniques and Applications
- Bacteriophages and microbial interactions
- Metabolism, Diabetes, and Cancer
- Hippo pathway signaling and YAP/TAZ
- Genomics and Phylogenetic Studies
- Metalloenzymes and iron-sulfur proteins
Center for Theoretical Biological Physics
2016-2025
Rice University
2016-2025
Yale University
2024
Northeastern University
2022
Universidade Estadual Paulista (Unesp)
2020
University of Houston
2019
Dan L Duncan Comprehensive Cancer Center
2019
Baylor College of Medicine
2004-2019
Astronomy and Space
2013-2018
University of California, San Diego
2004-2013
Abstract The understanding, and even the description of protein folding is impeded by complexity process. Much this can be described understood taking a statistical approach to energetics conformation, that is, energy landscape. landscape explains when why unique behaviors, such as specific pathways, occur in some proteins more generally distinction between processes common all sequences those peculiar individual sequences. This also gives new, quantitative insights into interpretation...
The similarity in the three-dimensional structures of homologous proteins imposes strong constraints on their sequence variability. It has long been suggested that resulting correlations among amino acid compositions at different positions can be exploited to infer spatial contacts within tertiary protein structure. Crucial this inference is ability disentangle direct and indirect correlations, as accomplished by recently introduced direct-coupling analysis (DCA). Here we develop a...
In biological and chemical electron transfer, a nuclear reaction coordinate is coupled to other and/or ‘‘solvent’’ coordinates. This coupling, or friction, if strong enough, may substantially slow down motion along the coordinate, thus vitiate assumption of transfer being nonadiabatic with respect nuclei. Here, simple, fully quantum mechanical model for using one mode treatment which incorporates this coupling studied. Path integral methods are used study dependence rate on limits moderate...
The rate of long-distance electron transfer in proteins rapidly decreases with distance, which is indicative an tunneling process. Calculations predict that the distance dependence native controlled by protein's structural motif. helix and sheet content a protein tertiary arrangement these secondary units define electronic coupling protein. calculations use pathway model applied previously success to ruthenated proteins. analysis ranks average decay constant for identifies amino acids are...
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, has not been visualized vivo, and thus, its functional impact energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by process requires cohesin ATPases. Once formed, however, loops compartments maintained for hours without energy input. Strikingly, ATP, observe emergence hundreds CTCF-independent link regulatory DNA. We also identify architectural...
Experimental information on the structure and dynamics of molten globules gives estimates for energy landscape's characteristics folding highly helical proteins, when supplemented by a theory helix-coil transition in collapsed heteropolymers. A law corresponding states relating simulations small lattice models to real proteins possessing many more degrees freedom results. This correspondence reveals parallels between "minimalist" results recent experimental degree native character state...
Significance Epithelial–mesenchymal transitions play crucial roles in embryonic development, wound healing, and cancer metastasis. It is clearly of interest to quantitatively understand the core circuitry that takes input from cell’s environment perform this cell-fate decision. We devised a unique model microRNA (miR)-based coupled chimeric modules underlying circuit; effort utilizes theoretical framework for treating miR dynamics. show miR-200/ZEB module functions as ternary switch,...
Large-scale motions of biomolecules involve linear elastic deformations along low-frequency normal modes, but for function nonlinearity is essential. In addition, unlike macroscopic machines, biological machines can locally break and then reassemble during function. We present a model global structural transformations, such as allostery, that large-scale motion possible partial unfolding, illustrating the method with conformational transition adenylate kinase. Structural deformation between...
The interplay between structure-search of the native structure and desolvation in protein folding has been explored using a minimalist model. These results support mechanism where most structural formation is achieved before water expelled from hydrophobic core. This view integrates expulsion effects into funnel energy landscape theory folding. Comparisons to experimental are shown for SH3 protein. After transition, near-native intermediate with partially solvated core found. transition...
The quantitative description of model protein folding kinetics using a diffusive collective reaction coordinate is examined. Direct kinetics, diffusional coefficients and free energy profiles are determined from Monte Carlo simulations 27-mer, 3 letter code lattice model, which corresponds roughly to small helical protein. Analytic calculations, simple rate theory, agree extremely well with the full simulation results. Folding in this system best seen as diffusive, funnel-like process.
Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Go) models utilize the funneled energy landscape theory of protein folding to provide an understanding both long scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our short high energetic structural resolution. Thus, atomic details included be used bridge between these two approaches. We report robustness mechanisms in one such all-atom model. Results for B domain A,...
Significance Chromatin consists of DNA and hundreds proteins that interact with the genetic material. In vivo, chromatin folds into nonrandom structures. The physical mechanism leading to these characteristic conformations, however, remains poorly understood. Here, we introduce a model generates chromosome conformations by using idea can be subdivided types based on its biochemical interactions. types, which are distinct from sequence, partially epigenetically controlled change during cell...
Significance The presence of heterogeneous subsets cancer stem cells (CSCs) remains a clinical challenge. These often occupy different regions in the primary tumor and have varied epithelial–mesenchymal phenotypes. Here, we devise theoretical framework to investigate how microenvironment (TME) modulates this spatial patterning. We find that gradient EMT-inducing signal, coupled with juxtacrine Notch-JAG1 signaling triggered by inflammatory cytokines TME, explains heterogeneity. Finally,...
Molecular dynamics simulations with coarse-grained or simplified Hamiltonians have proven to be an effective means of capturing the functionally important long-time and large-length scale motions proteins RNAs. Originally developed in context protein folding, structure-based models (SBMs) since been extended probe a diverse range biomolecular processes, spanning from RNA folding functional transitions molecular machines. The hallmark feature model is that part, all, potential energy function...
Metabolic plasticity enables cancer cells to switch their metabolism phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) during tumorigenesis metastasis. However, it is still largely unknown how orchestrate gene regulation balance OXPHOS activities. Previously, by modeling the of we have reported that can acquire a stable hybrid metabolic state in which both be used. Here, comprehensively characterize activity, establish theoretical framework coupling with pathways. Our...
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays crucial role during cancer progression. Here we utilized systems biology approach decipher regulatory principle and OXPHOS. Integrating information from literature, constructed network genes metabolites, which...
We introduce a theoretical framework that exploits the ever-increasing genomic sequence information for protein structure prediction. Structure-based models are modified to incorporate constraints by large number of non-local contacts estimated from direct coupling analysis (DCA) co-evolving sequences. A simple hybrid method, called DCA-fold, integrating DCA with an accurate knowledge local (e.g., secondary structure) is sufficient fold proteins in range 1–3 Å resolution.