A5019517261- Protein Structure and Dynamics
- Enzyme Structure and Function
- Estrogen and related hormone effects
- Mass Spectrometry Techniques and Applications
- Circadian rhythm and melatonin
- Ionic liquids properties and applications
- Analytical Chemistry and Chromatography
- Spectroscopy and Quantum Chemical Studies
- Various Chemistry Research Topics
- Enzyme Catalysis and Immobilization
- Chemical and Physical Properties in Aqueous Solutions
- Sleep and related disorders
- Computational Drug Discovery Methods
- Stress Responses and Cortisol
- Receptor Mechanisms and Signaling
- Menstrual Health and Disorders
- Inorganic and Organometallic Chemistry
- Bacteriophages and microbial interactions
- Bacillus and Francisella bacterial research
- Metabolomics and Mass Spectrometry Studies
- Advanced Biosensing Techniques and Applications
- Peroxisome Proliferator-Activated Receptors
- Lipid Membrane Structure and Behavior
- Thermal and Kinetic Analysis
- Matrix Theory and Algorithms
Universidade Estadual de Campinas (UNICAMP)
2015-2025
University of California, San Diego
2006-2023
National Health Insurance Fund
2023
National Institutes of Health
2023
Circadian (United States)
2023
VA San Diego Healthcare System
2023
Centro Universitário da Cidade
2020
Pontifícia Universidade Católica de Campinas
2016-2019
Virginia Commonwealth University
2019
Hospital de Clínicas da Unicamp
2019
Abstract Adequate initial configurations for molecular dynamics simulations consist of arrangements molecules distributed in space such a way to approximately represent the system's overall structure. In order that are not disrupted by large van der Waals repulsive interactions, atoms from different must keep safe pairwise distances. Obtaining arrangement can be considered packing problem: Each type molecule satisfy spatial constraints related geometry system, and distance between greater...
Molecular Dynamics is a powerful methodology for the comprehension at molecular level of many chemical and biochemical systems. The theories techniques developed structural thermodynamic analyses are well established, software packages available. However, designing starting configurations dynamics can be cumbersome. Easily generated regular lattices used when simple liquids or mixtures studied. complex mixtures, polymer solutions solid adsorbed (for example) this approach inefficient, it...
The analysis of structural mobility in molecular dynamics plays a key role data interpretation, particularly the simulation biomolecules. most common measures computed from simulations are Root Mean Square Deviation (RMSD) and Fluctuations (RMSF) structures. These after alignment atomic coordinates each trajectory step to reference structure. This rigid-body is not robust, sense that if small portion structure highly mobile, RMSD RMSF increase for all atoms, resulting possibly poor...
Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) γ to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure PPARγ ligand binding domain (LBD) and found the pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). verified MCFAs (C8–C10) bind LBD vitro showed they low-potency partial agonists...
Many algorithms exist for protein structural alignment, based on internal coordinates or explicit superposition of the structures. These methods are usually successful detecting similarities. However, current practical seldom supported by convergence theories. In particular, although goal each algorithm is to maximize some scoring function, there no method that theoretically guarantees score maximization. A with solid properties would be useful refinement folding maps, and development new...
Nuclear receptors are important targets for pharmaceuticals, but similarities between family members cause difficulties in obtaining highly selective compounds. Synthetic ligands that thyroid hormone (TH) receptor beta (TRbeta) vs. TRalpha reduce cholesterol and fat without effects on heart rate; thus, it is to understand TRbeta-selective binding. Binding of 3 (GC-1, KB141, GC-24) characterized at the atomic level; preferential binding depends a nonconserved residue (Asn-331beta) TRbeta...
Preferential solvation is a fundamental parameter for the interpretation of solubility and solute structural stability. The molecular basis solute-solvent interactions can be obtained through distribution functions, thermodynamic connection to experimental data depends on computation integrals, specifically Kirkwood-Buff integrals determination preferential interactions. Standard radial however, are not convenient study complex, nonspherical solutes, as proteins. Here we show that...
This study examines the influence of cation hydrophobicity on protein solvation in aqueous solutions Ionic Liquids. Ubiquitin structures and thermodynamics systems with 1-ethyl-3-methylimidazolium ([EMIM]⁺) 1-butyl-3-methylimidazolium ([BMIM]⁺) are studied using molecular dynamics simulations, Minimum-Distance distribution functions, Kirkwood-Buff theory solvation. At low concentrations, larger alkyl chain leads to enhanced water exclusion increased accumulation [BMIM]⁺ at surface relative...
Understanding how osmolytes influence protein folding is fundamental in biology and biotechnology. We developed a computational pipeline to investigate the structural thermodynamic effects of across landscape: Using coarse-grained simulations generate ensembles, we then employed atomistic explore each conformation aqueous solutions urea TMAO. Minimum-distance distribution functions Kirkwood-Buff solvation theory provide unprecedented details on structures thermodynamics. studied two model...
This study investigates the utilization of squid pen waste through a biocompatible ionic liquid approach, focusing on choline acetate, [Ch][OAc]. effectively extracts over 80 wt % protein from waste. To optimize extraction process, factorial design experiments was employed to achieve recovery 75% at an estimated purity 86%, along with highly acetylated, crystalline β-chitin up 95%. The extracted subsequently used create biocomposite films α- and β-chitosan, demonstrating impressive tensile...
Steered molecular dynamics simulations of ligand dissociation from Thyroid hormone receptors indicate that is favored via rearrangements in a mobile part the LBD comprising H3, loop between H1 and H2, nearby β-sheets, contrary to current models which H12 mostly involved. Dissociation facilitated this path by interaction hydrophilic with external water molecules, suggesting strategies enhance binding affinity.
Abstract Background Thyroid receptors, TRα and TRβ, are involved in important physiological functions such as metabolism, cholesterol level heart activities. Whereas metabolism increase lowering could be achieved by TRβ isoform activation, activation affects rates. Therefore, β-selective thyromimetics have been developed promising drug-candidates for treatment of obesity elevated level. GC-1 [3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)-phenoxy acetic acid] has ability to lower LDL with...
Estrogen Receptor (ER) is an important target for pharmaceutical design. Like other ligand-dependent transcription factors, hormone binding regulates ER transcriptional activity. Nevertheless, the mechanisms by which ligands enter and leave ERs nuclear receptors remain poorly understood. Here, we report results of locally enhanced sampling molecular dynamics simulations to identify dissociation pathways two [the natural 17beta-estradiol (E(2)) selective modulator raloxifene (RAL)] from human...
Thyroid hormone receptors (TR) are hormone-dependent transcription regulators that play a major role in human health, development, and metabolic functions. The thyroid resistance syndrome, diabetes, obesity, some types of cancer just few examples important diseases related to TR malfunctioning, particularly impaired binding. Ligand binding dissociation from the receptor ultimately control gene and, thus, detailed knowledge release mechanisms fundamental for comprehension receptor's...
Thyroid hormone receptors (TRs) are ligand-gated transcription factors with critical roles in development and metabolism. Although x-ray structures of TR ligand-binding domains (LBDs) agonists available, comparable without ligand (apo-TR) or antagonists not. It remains important to understand apo-LBD conformation the way that it rearranges ligands develop better pharmaceuticals. In this study, we conducted hydrogen/deuterium exchange on LBDs agonist (T(3)) antagonist (NH3). Both reduce...
Unveiling the mechanisms of energy relaxation in biomolecules is key to our understanding protein stability, allostery, intramolecular signaling, and long-lasting quantum coherence phenomena at ambient temperatures. Yet, relationship between pathways transfer functional role residues involved remains largely unknown. Here, we develop a simulation method mapping out that are highly efficient relaxing an initially localized excess vibrational perform site-directed mutagenesis assays assess...
Abstract Thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily ligand-activated transcription factors involved in cell differentiation, growth, and homeostasis. Although X-ray structures many ligand-binding domains (LBDs) reveal that ligand binds within hydrophobic core pocket, a few studies suggest possibility ligands binding to other sites. Here, we report new x-ray crystallographic structure TR-LBD shows second site for T3 T4 located between H9, H10, H11 TRα LBD...
Simulating huge biomolecular complexes of million atoms at relevant biological time scales is becoming accessible to the broad scientific community. That proves be crucial for urgent responses against emergent diseases in real time. Yet, there are still issues sort regarding system setup so that molecular dynamics (MD) simulations can run a simple and standard way. Here, we introduce an optimized pipeline building simulating enveloped virus-like particles (VLP). First, membrane packing...
Supercritical carbon dioxide is a promising green-chemistry solvent for many enzyme-catalyzed chemical reactions, yet the striking stability of some enzymes in such unconventional environments not well understood. Here, we investigate stabilization Candida antarctica Lipase B (CALB) supercritical dioxide–water biphasic systems using molecular dynamics simulations. The preservation enzyme structure and optimal activity depend on presence small amounts water dispersing medium. When protein at...
As far as more complex systems are being accessible for quantum chemical calculations, the reliability of algorithms used becomes increasingly important. Trust-region strategies comprise a large family optimization that incorporates both robustness and applicability great variety problems. The objective this work is to provide basic algorithm an adequate theoretical framework application globally convergent trust-region methods electronic structure calculations. Closed shell restricted...