Modeling of macromolecular structures and interactions represents an important challenge for computational biology, involving different time length scales. However, this task can be facilitated through the use coarse-grained (CG) models, which reduce number degrees freedom allow efficient exploration complex conformational spaces. This article presents a new CG protein model named SIRAH, developed to work with explicit solvent capture sequence, temperature, ionic strength effects in...

We report on the fate of nucleic acids conformation in gas phase as sampled using native mass spectrometry coupled to ion mobility spectrometry. On basis several successful reports for proteins and their complexes, technique has become popular structural biology, survival becomes more taken granted. Surprisingly, we found that DNA RNA duplexes, at electrospray charge states naturally obtained from solution conditions (≥100 mM aqueous NH4OAc), are significantly compact compared canonical...

Biological processes occur on space and time scales that are often unreachable for fully atomistic simulations. Therefore, simplified or coarse grain (CG) models the theoretical study of these systems frequently used. In this context, accurate description solvation properties remains an important challenging field. present work, we report a new CG model based transient tetrahedral structures observed in pure water. Our representation lumps approximately 11 WATer molecules into FOUR...

Transient receptor potential (TRP) ion channels constitute a notable family of cation involved in the ability an organisms to detect noxious mechanical, thermal, and chemical stimuli that give rise perception pain, taste, changes temperature. One most experimentally studied agonist TRP is capsaicin, which responsible for burning sensation produced when chili pepper contact with organic tissues. Thus, understanding how this molecule interacts regulates essential high impact pharmacological...

We have previously shown that 5' halves from tRNAGlyGCC and tRNAGluCUC are the most enriched small RNAs in extracellular space of human cell lines, especially non-vesicular fraction. Extracellular believed to require protection by either encapsulation vesicles or ribonucleoprotein complex formation. However, deproteinization tRNA does not affect their retention size-exclusion chromatography. Thus, we considered alternative explanations for stability. In-silico analysis sequence these...

Accurate simulation of biomolecular systems requires the consideration solvation effects. The arrangement and dynamics water close to a solute are strongly influenced by itself. However, as solute-solvent distance increases, properties tend those bulk liquid. This suggests that regions can be treated at coarse grained (CG) level, while keeping atomistic details around solute. Since represents about 80% any biological system, this approach may offer significant reduction in computational cost...

Dual-resolution approaches for molecular simulations combine the best of two worlds, providing atomic details in regions interest and coarser but much faster descriptions less-relevant parts systems. Given abundance water biomolecular systems, reducing computational cost simulating bulk without perturbing solute's properties is a very attractive strategy. Here we show that coarse-grained model called WatFour (WT4) can be combined with any three most used models atomistic (SPC, TIP3P, SPC/E)...

Abstract Coarse‐grained (CG) models for macromolecules have become a standard in the study of biological systems, overcoming limitations size and time scales encountered by atomistic molecular dynamics simulations. Just as any biomolecular ensemble, water CG plays key role mediating intermolecular intramolecular interactions. However, owing to highly nontrivial properties water, important simplifications been commonly used treat solvation effects. Recent developments are overviewed,...

Although chemically close to DNA, RNA can adopt a wide range of structures from regular helices complex globular conformations, showing complexity similar that proteins. The determination the structure molecules, crucial for functional understanding, is severely handicapped by their size and flexibility, which makes systematic use experimental approaches difficult. Simulation techniques are also suffering very severe problems related accuracy methods ability sample large conformational...

While DNA is mostly a primary carrier of genetic information and displays regular duplex structure, RNA can form very complicated conserved 3D structures displaying large variety functions, such as being an intermediary the information, translating into protein machinery cell, or even acting chemical catalyst. At base functional diversity subtle balance between different backbone, nucleobase, ribose conformations, finely regulated by combination hydrogen bonds stacking interactions. Although...

Transient receptor potential (TRP) ion channels are important pharmacological targets because of their role in the perception pain, and so, understanding chemical regulation is essential for development analgesic drugs. Among currently known TRP channel agonists, capsaicin, active compound chili pepper, probably most exhaustively studied. The availability three-dimensional structure vanilloid 1 (TRPV1) has fueled computational studies revealing molecular details capsaicin binding modes....

Cholesterol is a major component of mammalian plasma membranes that not only affects the physical properties lipid bilayer but also function many membrane proteins including G protein-coupled receptors. The oxytocin receptor (OXTR) involved in parturition and lactation mammals their emotional social behaviors. acts on OXTR as an allosteric modulator inducing high-affinity state for orthosteric ligands through molecular mechanism has yet to be determined. Using ion channel-coupled technology,...

In combination with other spectroscopy, microscopy, and scattering techniques, neutron reflectivity is a powerful tool to characterize biological systems. Specular reflection of neutrons provides structural information at the nanometer subnanometer length scales, probing composition organization layered materials. Currently, analysis data involves several simplifying assumptions about structure sample under study, affecting extraction interpretation from experimental data. Computer...

Potassium channels are of paramount physiological and pathological importance therefore constitute significant drug targets. One the keys to rationalize way drugs modulate ion is understand ability such small molecules access their respective binding sites, from which they can exert an activating or inhibitory effect. Many computational studies have probed energetics permeation, mechanisms voltage gating, but little known about role fenestrations as possible mediators entry in potassium...

The lipopeptide surfactin produced by certain strains of Bacillus subtillis is a potent biosurfactant with high amphiphilicity and strong tendency for self-aggregation. Surfactin possesses number valuable biological properties such as antiviral, antibacterial, antifungal, hemolytic activities. Owing to these properties, in addition the general advantages biosurfactants over synthetic surfactants, has potential biotechnological biomedical applications. Here, aggregation solution together its...

Voltage-gated potassium channels of the Kv1 family play a crucial role in generation and transmission electrical signals excitable cells affecting neuronal cardiac activities. Small-molecule blockage these has been proposed to occur via cooperative mechanism involving two main blocking sites: inner-pore site located below selectivity filter, side-pocket cavity between pore voltage sensor. Using 0.5 μs molecular dynamics simulation trajectories complemented by docking calculations, potential...

The characterization of the conformational landscape RNA backbone is rather complex due to ability assume a large variety conformations. These conformations can be depicted by pseudotorsional angles linking atoms, from which Ramachandran-like plots built. We explore here different definitions these angles, finding that most accurate ones are traditional η (eta) and θ (theta) represent relative position atoms P C4'. distribution - in known experimental structures, comparing space generated...

veriNA3d is an R package for the analysis of nucleic acids structural data, with emphasis in complex RNA structures. In addition to single-structure analyses, also implements functions handle whole datasets mmCIF/PDB structures that could be retrieved from public/local repositories. Our aims fill a gap data mining produce flexible and high throughput databases.http://mmb.irbbarcelona.org/gitlab/dgallego/veriNA3d.Supplementary are available at Bioinformatics online.

ABSTRACT Native mass spectrometry coupled to ion mobility is a promising tool for structural biology. Intact complexes can be transferred the spectrometer and, if native conformations survive, collision cross sections give precious information on structure of each species in solution. Based several successful reports proteins and their complexes, conformation survival becomes more taken granted. Here we report fate nucleic acids gas phase. Disturbingly, found that DNA RNA duplexes, at...