Interaction of Statherin-Derived Peptide with the Surface of Hydroxyapatite: Perspectives Based on Molecular Dynamics Simulations.

Introduction: Statherin-derived peptide (StatpSpS) has shown promise against erosive tooth wear. To elucidate its interaction with the hydroxyapatite (HAP) surface, the mechanism related to adsorption of this peptide with HAP was investigated through nanosecond-long all-atom molecular dynamics simulations.

Methods: StatpSpS was positioned parallel to the HAP surface in 2 orientations: 1 - neutral and negative residues facing the surface and 2 - positive residues facing the surface.

Comparative docking and molecular dynamics studies of molnupiravir (EIDD-2801): implications for novel mechanisms of action on influenza and SARS-CoV-2 protein targets.

Molnupiravir (EIDD-2801) (MLN) is an oral antiviral drug for COVID-19 treatment, being integrated into viral RNA through RNA-dependent RNA polymerase (RdRp). Upon ingestion, MLN is transformed into two active metabolites: β-d-N-hydroxycytidine (NHC) (EIDD-1931) in the host plasma, and EIDD-1931-triphosphate (MTP) within the host cells. However, recent studies provide increasing evidence of MLN's interactions with off-target proteins beyond the viral genome, suggesting that the complete mechanisms of action of MLN remain unclear.

A Family of Bisnaphthyl C-Symmetric and Asymmetric Clefts: Synthesis, Solid-State Structure, and Calculation of the Interplanar Angle.

The synthesis of a new family of naphthalenoid C-symmetric clefts has been realized through a four-step synthetic sequence giving three C-symmetric clefts and a rare nonsymmetric example. Subsequently, stereoselective reduction of the carbonyl groups at C-8 and C-16 then provides cleft molecules with hydrogen bonding potential. Using single-crystal X-ray and computational analysis, the cleft angle of the dione has been determined.

Antioxidant and Anticancer Potential of the New Cu(II) Complexes Bearing Imine-Phenolate Ligands with Pendant Amine N-Donor Groups.

Cu(II) complexes bearing NNO-donor Schiff base ligands (, ) have been synthesized and characterized. The single crystal X-ray analysis of the complex revealed that a mononuclear and a dinuclear complex co-crystallize in the solid state. The electronic structures of the complexes are optimized by Density Functional Theory (DFT) calculations.

Molecular evolution and structural analyses of the spike glycoprotein from Brazilian SARS-CoV-2 genomes: the impact of selected mutations.

The COVID-19 pandemic caused by SARS-CoV-2 has reached by February 2022 more than 380 million cases and 5.5 million deaths worldwide since its beginning in late 2019, leading to enhanced concern in the scientific community and the general population. One of the most important pieces of this host-pathogen interaction is the spike protein, which binds to the hACE2 cell receptor, mediates the membrane fusion and is the major target of neutralizing antibodies against SARS-CoV-2.

Molecular dynamics simulations of structural and dynamical aspects of DNA hydration water.

Water is a remarkable liquid, both because of it is intriguing but also because of its importance. Water plays a key role on the structure and function of biological molecules, but on the other hand also the structure and dynamics of water are deeply influenced by its interactions with biological molecules, specially at low temperatures, where water's anomalies are enhanced. Here we present extensive molecular dynamics simulations of water hydrating a oligonucleotide down to very low temperatures (supercooled water), comparing four water models and analyzing the water structure and dynamics in different domains: water in the minor groove, water in the major groove and bulk water.

Computational studies of polyurethanases from Pseudomonas.

Polyurethanes (PU) are multifunctional polymers, used in automotive industry, in coatings, rigid and flexible foams, and also in biomimetic materials. In the same way as all plastic waste, the incorrect disposal of these materials leads to the accumulation of polyurethanes in the environment. To reduce the amount of waste as well as add value to degradation products, bioremediation methods have been studied for waste management of PU.

analysis of the interactions of certain flavonoids with the receptor-binding domain of 2019 novel coronavirus and cellular proteases and their pharmacokinetic properties.

Coronavirus Disease 2019 (COVID-19) has infected more than thirty five million people worldwide and caused nearly 1 million deaths as of October 2020. The microorganism causing COVID-19 was named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV). The aim of this study was to investigate the interactions of twenty-three phytochemicals belonging to different flavonoid subgroups with the receptor binding domain (RBD) of the spike glycoprotein of 2019-nCoV, and cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B and L (CatB/L)].

Why Does the Novel Coronavirus Spike Protein Interact so Strongly with the Human ACE2? A Thermodynamic Answer.

The SARS-CoV-2 pandemic is the biggest health concern today, but until now there is no treatment. One possible drug target is the receptor binding domain (RBD) of the coronavirus' spike protein, which recognizes the human angiotensin-converting enzyme 2 (hACE2). Our in silico study discusses crucial structural and thermodynamic aspects of the interactions involving RBDs from the SARS-CoV and SARS-CoV-2 with the hACE2.

The role of osmolytes in the temperature-triggered conformational transition of poly(N-vinylcaprolactam): an experimental and computational study.

Biomedical industries are widely exploring the use of thermo-responsive polymers (TRPs) in the advanced development of drug delivery and in many other pharmaceutical applications. There is a great need to investigate the use of less toxic and more (bio-)compatible TRPs employing several additives, which could modify the conformational transition behavior of TRPs in aqueous solution. To move forward in this aspect, we have chosen the less toxic bio-based polymer poly(N-vinylcaprolactam) (PVCL) and three different methylamine-based osmolytes, trimethylamine N-oxide (TMAO), betaine and sarcosine, in order to investigate their particular interactions with the polymer segments in PVCL and therefore the corresponding changes in the thermo-responsive conformational behavior.

Growth Mechanism of Gold Nanorods: the Effect of Tip-Surface Curvature As Revealed by Molecular Dynamics Simulations.

An understanding of the anisotropic growth mechanism of gold nanorods (AuNRs) during colloidal synthesis is critical for controlling the nanocrystal size and shape and thus has implications in tuning the properties for applications in a wide range of research and technology fields. In order to investigate the role of the cetyltrimethylammonium bromide (CTAB) coating in the anisotropic growth mechanism of AuNRs, we used molecular dynamics (MD) simulations and built a computational model that considered explicitly the effect of the curvature of the gold surface on CTAB adsorption and therefore differentiated between the CTAB arrangements on flat and curved surfaces, representing the lateral and tip facets of growing AuNRs, respectively. We verified that on a curved surface, a lower CTAB coverage density and larger intermicellar channels are generated compared to those on a flat surface.

Single molecule force spectroscopy of a streptomycin-binding RNA aptamer: An out-of-equilibrium molecular dynamics study.

Here, we investigate the unfolding behavior of a streptomycin-binding ribonucleic acid (RNA) aptamer under application of force in shear geometry. Using Langevin out-of-equilibrium simulations to emulate the single-molecule force spectroscopy (SMFS) experiment, we were able to understand the hierarchical unfolding process that occurs in the RNA molecule under application of stretching force and the influence of streptomycin modifying this unfolding. Subsequently, the application of the Jarzynski equality to the force profiles obtained in the pulling simulations shows that the free energies for individual systems and the difference of unfolding free energy upon streptomycin binding to the RNA free aptamer are in fair agreement with the experimental values, obtained through SMFS by Nick et al.

Polyurethanases: Three-dimensional structures and molecular dynamics simulations of enzymes that degrade polyurethane.

The global production of plastics increases every year, because these materials are widely used in several segments of modern life. Polyurethanes are a very important class of polymers, used in many areas of everyday life, from automotive equipments to mattresses. The waste management usually involves accumulation in landfills, incineration, and reuse processes.

Prion protein conversion triggered by acidic condition: a molecular dynamics study through different force fields.

Prions are proteins that cause a group of invariably fatal neurodegenerative diseases, one of the most known being bovine spongiform encephalopathy. The three-dimensional structure of PrP , the altered isoform of the prion protein, has not been fully elucidated yet, and studies on prion conversion mechanisms must rely on hypothetical β-rich structures. Experimental and computational studies indicate that the use of low pH is capable to produce a gain of β-structure content in the otherwise unstructured N-terminal region.

SERCA plays a crucial role in the toxicity of a betulinic acid derivative with potential antimalarial activity.

Malaria is one of the most significant infectious diseases that affect poor populations in tropical areas throughout the world. Plants have been shown to be a good source for the development of new antimalarial chemotherapeutic agents, as shown for the discovery of quinine and artemisinin derivatives. Our research group has been working with semisynthetic triterpene derivatives that show potential antimalarial activity toward different strains of Plasmodium falciparum by specifically modulating calcium pathways in the parasite.

Molecular dynamics study of the LCST transition in aqueous poly(N-n-propylacrylamide).

The breadth of technological applications of smart polymers relies on the possibility of tuning their molecular structure to respond to external stimuli. In this context, N-substituted acrylamide-based polymers are widely studied thermoresponsive polymers. Poly(N-n-propylacrylamide) (PNnPAm), which is a structural isomer of the poly(N-isopropylacrylamide) (PNIPAm) exhibits however, a lower phase transition in aqueous solution.

Conjugation with polyamines enhances the antitumor activity of naphthoquinones against human glioblastoma cells.

Glioblastoma multiform (GBM) is the most common and devastating type of primary brain tumor, being considered the deadliest of human cancers. In this context, extensive efforts have been undertaken to develop new drugs that exhibit both antiproliferation and antimetastasis effects on GBM. 1,4-Naphthoquinone (1,4-NQ) scaffold has been found in compounds able to inhibit important biological targets associated with cancer, which includes DNA topoisomerase, Hsp90 and monoamine oxidase.

Structure and mobility of water confined in AlPO-54 nanotubes.

We performed molecular dynamics simulations of water confined within AlPO-54 nanotubes. AlPO-54 is an artificial material made of AlO and of PO in tetrahedra arranged in a periodic structure forming pores of approximately 1.3 nm in diameter.

Ru-Catalyzed Estragole Isomerization under Homogeneous and Ionic Liquid Biphasic Conditions.

The isomerization of estragole to -anethole is an important reaction and is industrially performed using an excess of NaOH or KOH in ethanol at high temperatures with very low selectivity. Simple Ru-based transition-metal complexes, under homogeneous, ionic liquid (IL)-supported (biphasic) and "solventless" conditions, can be used for this reaction. The selectivity of this reaction is more sensitive to the solvent/support used than the ligands associated with the metal catalyst.

Organocatalytic Imidazolium Ionic Liquids H/D Exchange Catalysts.

Simple 1,2,3-trialkylimidazolium cation associated with basic anions, such as hydrogen carbonate, prolinate, and imidazolate, is an active catalyst for the H/D exchange reaction of various substrates using CDCl as D source, without the addition of any extra bases or metal. High deuterium incorporation (up to 49%) in acidic C-H bonds of ketone and alkyne substrates (pK from 18.7 to 28.

Effects of stereochemistry and copolymerization on the LCST of PNIPAm.

Poly(N-isopropylacrylamide) (PNIPAm) is a smart polymer that presents a lower critical transition temperature (LCST) of 305 K. Interestingly, this transition point falls within the range of the human body temperature, making PNIPAm a highly suitable candidate for bio-medical applications. However, it is sometimes desirable to have a rather flexible tuning of the LCST of these polymers to further increase their range of applications.

Adaptive resolution simulation of oligonucleotides.

Nucleic acids are characterized by a complex hierarchical structure and a variety of interaction mechanisms with other molecules. These features suggest the need of multiscale simulation methods in order to grasp the relevant physical properties of deoxyribonucleic acid (DNA) and RNA using in silico experiments. Here we report an implementation of a dual-resolution modeling of a DNA oligonucleotide in physiological conditions; in the presented setup only the nucleotide molecule and the solvent and ions in its proximity are described at the atomistic level; in contrast, the water molecules and ions far from the DNA are represented as computationally less expensive coarse-grained particles.