A5020634590- Protein Structure and Dynamics
- Force Microscopy Techniques and Applications
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Biochemical and Structural Characterization
- Microbial Metabolic Engineering and Bioproduction
- Bacteriophages and microbial interactions
- SARS-CoV-2 and COVID-19 Research
- Lipid Membrane Structure and Behavior
- Spectroscopy and Quantum Chemical Studies
- Biofuel production and bioconversion
- Monoclonal and Polyclonal Antibodies Research
- Bacterial biofilms and quorum sensing
- Mechanical and Optical Resonators
- Biotin and Related Studies
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- Cellular Mechanics and Interactions
- Mass Spectrometry Techniques and Applications
- Computational Drug Discovery Methods
- Advanced Electron Microscopy Techniques and Applications
- Crystallography and molecular interactions
- Scientific Computing and Data Management
- Fullerene Chemistry and Applications
- Trypanosoma species research and implications
Auburn University
2020-2025
University of Illinois Urbana-Champaign
2013-2023
Translational Therapeutics (United States)
2020
University of Pennsylvania
2020
Energy Biosciences Institute
2015-2016
Instituto Nacional de Metrologia, Qualidade e Tecnologia
2011-2013
Universidade Federal do Rio de Janeiro
2009-2012
Instituto de Biofísica Carlos Chagas Filho
2011
Centro Brasileiro de Pesquisas Físicas
2007-2009
Universidade Estadual de Londrina
2005
NAMDis a molecular dynamics program designed for high-performance simulations of very large biological objects on CPU- and GPU-based architectures. NAMD offers scalable performance petascale parallel supercomputers consisting hundreds thousands cores, as well inexpensive commodity clusters commonly found in academic environments. It is written C++ leans Charm++ optimal low-latency versatile, multipurpose code that gathers state-of-the-art algorithms to carry out apt thermodynamic ensembles,...
Abstract The proper functioning of biomolecules in living cells requires them to assume particular structures and undergo conformational changes. Both biomolecular structure motion can be studied using a wide variety techniques, but none offers the level detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD VMD, we have created robust, user-friendly software, QwikMD, which enables novices experts alike address biomedically relevant...
High resilience to mechanical stress is key when pathogens adhere their target and initiate infection. Using atomic force microscopy-based single-molecule spectroscopy, we explored the stability of prototypical staphylococcal adhesin SdrG, which targets a short peptide from human fibrinogen β. Steered molecular dynamics simulations revealed, spectroscopy experiments confirmed, mechanism by this complex withstands forces over 2 nanonewtons, regime previously associated with strength covalent...
Molecular interactions are essential for regulation of cellular processes from the formation multi-protein complexes to allosteric activation enzymes. Identifying residues and molecular features that regulate such is paramount understanding biochemical process in question, allowing suppression a reaction through drug interventions or optimization chemical using bioengineered molecules. In order identify important information pathways within complexes, dynamical network analysis method was...
Abstract Challenging environments have guided nature in the development of ultrastable protein complexes. Specialized bacteria produce discrete multi-component networks called cellulosomes to effectively digest lignocellulosic biomass. While network assembly is enabled by interactions with commonplace affinities, we show that certain cellulosomal ligand–receptor exhibit extreme resistance applied force. Here, characterize complex responsible for substrate anchoring Ruminococcus flavefaciens...
Here we employ single-molecule force spectroscopy with an atomic microscope (AFM) and steered molecular dynamics (SMD) simulations to reveal propagation pathways through a mechanically ultrastable multidomain cellulosome protein complex. We demonstrate new combination of network-based correlation analysis supported by AFM directional pulling experiments, which allowed us visualize stiff paths the complex along is transmitted. The results implicate specific force-propagation routes...
Macromolecules tend to respond applied forces in many different ways. Chemistry at high shear can be intriguing, with relatively soft bonds becoming very stiff specific force-loading geometries. Largely used bionanotechnology, an important case is the streptavidin (SA)/biotin interaction. Although SA's four subunits have same affinity, we find that required break SA/biotin bond depend strongly on attachment geometry. With AFM-based single-molecule force spectroscopy (SMFS), measured...
Can molecular dynamics simulations predict the mechanical behavior of protein complexes? decipher role domains unknown function in large macromolecular Here, we employ a wide-sampling computational approach to demonstrate that simulations, when carefully performed and combined with single-molecule atomic force spectroscopy experiments, can explain highly mechanostable complexes. As test case, studied previously unreported homologue from Ruminococcus flavefaciens called X-module-Dockerin...
Significance In the dynamic environment of airways, where SARS-CoV-2 infections are initiated by binding to human host receptor ACE2, mechanical stability viral attachment is a crucial fitness advantage. Using single-molecule force spectroscopy techniques, we mimic effect coughing and sneezing, thereby testing RBD:ACE2 interaction under physiological conditions. Our results reveal higher ACE2 compared SARS-CoV-1, causing possible assay sensitive blocking agents preventing bond formation. It...
Modeling and simulation of small molecules such as drugs biological cofactors have been both a major focus computational chemistry for decades growing need among biophysicists who seek to investigate the interaction different types ligands with biomolecules. Of particular interest in this regard are quantum mechanical (QM) calculations that used more accurately describe molecules, which can be heterogeneous structures chemistry, either purely QM or hybrid QM/molecular mechanics (MM)...
Novel site-specific attachment strategies combined with improvements of computational resources enable new insights into the mechanics monovalent biotin/streptavidin complex under load and forced us to rethink diversity rupture forces reported in literature. We discovered that mechanical stability this depends strongly on geometry which force is applied. By atomic microscopy-based single molecule spectroscopy we found unbinding biotin occur beyond 400 pN at loading rates 10 nN/s when...
Abstract Bacterial colonization of the human intestine requires firm adhesion bacteria to insoluble substrates under hydrodynamic flow. Here we report molecular mechanism behind an ultrastable protein complex responsible for resisting shear forces and adhering cellulose fibers in gut. Using single-molecule force spectroscopy (SMFS), FRET (smFRET), dynamics (MD) simulations, resolve two binding modes three unbinding reaction pathways a mechanically R. champanellensis ( Rc ) Dockerin:Cohesin...
Understanding binding epitopes involved in protein–protein interactions and accurately determining their structure are long-standing goals with broad applicability industry biomedicine. Although various experimental methods for epitope determination exist, these approaches typically low throughput cost-intensive. Computational have potential to accelerate predictions; however, recently developed artificial intelligence (AI)-based frequently fail predict of synthetic domains few natural...
Cellulosomes are polyprotein machineries that efficiently degrade cellulosic material. Crucial to their function scaffolds consisting of highly homologous cohesin domains, which serve a dual role by coordinating multiplicity enzymes as well anchoring the microbe its substrate. Here we combined two approaches elucidate mechanical properties main scaffold ScaA Acetivibrio cellulolyticus. A newly developed parallelized one-pot in vitro transcription–translation and protein pull-down protocol...
Mechanoactive proteins are essential for a myriad of physiological and pathological processes. Guided by the advances in single-molecule force spectroscopy (SMFS), we have reached molecular-level understanding how mechanoactive sense respond to mechanical forces. However, even SMFS has its limitations, including lack detailed structural information during force-loading experiments. That is where molecular dynamics (MD) methods shine, bringing atomistic details with femtosecond...
The bone sialoprotein-binding protein (Bbp) is a mechanoactive MSCRAMM expressed on the surface of Staphylococcus aureus that mediates adherence bacterium to fibrinogen-α (Fgα), component and dentine extracellular matrix host cell. Mechanoactive proteins like Bbp have key roles in several physiological pathological processes. Particularly, Bbp: Fgα interaction important formation biofilms, an virulence factor pathogenic bacteria. Here, we investigated mechanostability complex using silico...