Artificial Intelligence, Molecular Dynamics, and Beyond: Computational Insights In Cosmetics Research and Formulation Design.

The vast field of cosmetics is mainly explored through experimental methods, while computational tools find broader application in structuralbiology. The world of formulations remains relatively untouched or nondisclosed due to commercial interests. This work aims to better understand the applications of in silico methods in cosmetics research, at the molecular level, and how the recent work is advancing the state of the art.

AI, docking, and molecular dynamics to track the binding of structural peptides to different keratin models.

The present work shows a computational approach to assess the interactions of different nature-inspired peptides with hair keratin models. An updated keratin model was validated, and comparisons with previous models were traced, thereby highlighting the time-evolution of both the model and the in silico methods. Importantly, the computational methodology presented here allows for the study of peptide-protein interactions between unknown or unsolved structures.

Solvent-free synthesis of hydrophobic and amphiphilic esters using a chemically modified lipase from Thermomyces lanuginosus: a comparative study with native and immobilized forms.

Using lipases to catalyze the synthesis of the most differentiated type of compounds remains one of the major challenges among scientists. Seeking more economic and advantageous catalysts is a current goal of green chemistry. In this work, we demonstrate the potential of a chemically modified form of lipase from Thermomyces lanuginosus (cmLTL) for the synthesis of both hydrophobic (heptyl heptanoate, heptyl octanoate, heptyl decanoate, decyl heptanoate, decyl octanoate and decyl decanoate) and amphiphilic (2-(2-ethoxyethoxy)ethyl oleate and 2-(2-ethoxyethoxy)ethyl linoleate) esters, in bulk.

Golgi α-mannosidase: opposing structures of and novel human model using molecular dynamics simulations and docking at different pHs.

The search for Golgi α-mannosidase II (GMII) potent and specific inhibitors has been a focus of many studies for the past three decades since this enzyme is a key target for cancer treatment. α-Mannosidases, such as those from or Jack bean, have been used as functional models of the human Golgi α-mannosidase II (hGMII) because mammalian mannosidases are difficult to purify and characterize experimentally. Meanwhile, computational studies have been seen as privileged tools able to explore assertive solutions to specific enzymes, providing molecular details of these macromolecules, their protonation states and their interactions.

Synthesis of Novel 2,9-Disubstituted-6-morpholino Purine Derivatives Assisted by Virtual Screening and Modelling of Class I PI3K Isoforms.

The phosphatidylinositol-3 kinase (PI3K) pathway is one of the most frequently activated pathogenic signalling cascades in a wide variety of cancers. In the last 15 years, there has been an increase in the search for selective inhibitors of the four class I isoforms of PI3K, as they demonstrate better specificity and reduced toxicity in comparison to existing inhibitors. A ligand-based and target-based rational drug design strategy was employed to build a virtual library of 105 new compounds.

Addressing the Structural Organization of Silicone Alternatives in Formulations by Molecular Dynamics Simulations and a Novel Equilibration Protocol.

The world of cosmetics is an always-evolving field with constant updates on its formulation components. The current reality asks for an ever-increasing need for natural and sustainable replacements for synthetic compounds in all fields of modern consumer products. However, the research and development stages of finding these alternatives can be an expensive, time-consuming, and often wasteful process that turns this task into a laborious procedure.

Acetylation and phosphorylation processes modulate Tau's binding to microtubules: A molecular dynamics study.

The microtubule-associated protein Tau has its normal function impaired when undergoing post-translational modifications. In this work, molecular modelling techniques were used to infer the effects of acetylation and phosphorylation in Tau's overall conformation, electrostatics, and interactions, but mostly in Tau's ability to bind microtubules. Reported harmful Lys sites were mutated by its acetylated form, generating eight different acetylated Tau (aTau) analogues.

From groove binding to intercalation: unravelling the weak interactions and other factors modulating the modes of interaction between methylated phenanthroline-based drugs and duplex DNA.

Several antitumor drugs base their cytotoxicity on their capacity to intercalate between base pairs of DNA. Nevertheless, it has been established that the mechanism of intercalation of drugs in DNA starts with the prior groove binding mode of interaction of the drug with DNA. Sometimes, for some kind of flat small molecules, groove binding does not produce any cytotoxic effect and the fast transition of such flat small molecules to the cytotoxic intercalation mode is desirable.

Hofmeister effects on protein stability are dependent on the nature of the unfolded state.

The interpretation of a salt's effect on protein stability traditionally discriminates low concentration regimes (<0.3 M), dominated by electrostatic forces, and high concentration regimes, generally described by ion-specific Hofmeister effects. However, increased theoretical and experimental studies have highlighted observations of the Hofmeister phenomena at concentration ranges as low as 0.

The Structural Properties of Odorants Modulate Their Association to Human Odorant Binding Protein.

The binding of known odorant molecules to the human odorant-binding protein (hOBP) was evaluated Docking experiments elucidate the preferable binding site and binding affinity of odorant molecules to hOBP. The physicochemical properties molecular weight (MW), vapor pressure (Vp), hydrophobicity level (logP), number of double bonds (NºDB), degree of unsaturation (DoU) and the chemical classification, were selected for the study of odorant modulation. Here, these properties were analyzed concerning 30 pleasant and 30 unpleasant odorants, chosen to represent a wide variety of compounds and to determine their influence on the binding energy to hOBP.

Electrostatics of Tau Protein by Molecular Dynamics.

Tau is a microtubule-associated protein that promotes microtubule assembly and stability. This protein is implicated in several neurodegenerative diseases, including Alzheimer's. To date, the three-dimensional (3D) structure of tau has not been fully solved, experimentally.

Two Engineered OBPs with opposite temperature-dependent affinities towards 1-aminoanthracene.

Engineered odorant-binding proteins (OBPs) display tunable binding affinities triggered by temperature alterations. We designed and produced two engineered proteins based on OBP-I sequence: truncated OBP (tOBP) and OBP::GQ::SP-DS3. The binding affinity of 1-aminoanthracene (1-AMA) to these proteins revealed that tOBP presents higher affinity at 25 °C (kd = 0.

The effect of high-energy environments on the structure of laccase-polymerized poly(catechol).

The laccase polymerization of catechol was performed using different reactors namely a water bath (WB), an ultrasonic bath (US) and a high-pressure homogenizer (HPH). The total content of free OH and the MALDI-TOF spectra of polymers obtained demonstrated that reactions are favored in the presence of high-energy environments. Higher conversion yields and polymerization degrees (DP) were obtained after polymerization using US or HPH.

OBP fused with cell-penetrating peptides promotes liposomal transduction.

Cell-penetrating peptides (CPPs) have been applied as novel transport systems with the ability to facilitate the delivery of peptides, proteins, and oligonucleotides into cells. Herein, we designed different fusion proteins composed by pig odorant binding protein (OBP-I) and three CPPs, namely Tat, pVEC and Pep-1. A new methodology using liposomes as reservoirs and OBP:CPPs as carriers was developed as an advanced system to capture odorant molecules.

Modeling the secondary structures of the peptaibols antiamoebin I and zervamicin II modified with D-amino acids and proline analogues.

Antiamoebin I (AAM-I) and zervamicin II (Zrv-IIB) are peptaibols that exert antibiotic activity through the insertion/disruption of cell membranes. In this study, we investigated how the folding of these peptaibols are affected when some of their native residues are replaced with proline analogues and asymmetrical D-α,α-dialkyl glycines (two classes of noncanonical amino acids). Systematic substitutions of native Aib, Pro, Hyp, and Iva residues were performed to elucidate the folding properties of the modified peptaibols incorporating noncanonical residues.

Conformational and thermodynamic properties of non-canonical α,α-dialkyl glycines in the peptaibol Alamethicin: molecular dynamics studies.

In this work, we investigate the structure, dynamic and thermodynamic properties of noncanonical disubstituted amino acids (α,α-dialkyl glycines), also known as non-natural amino acids, in the peptaibol Alamethicin. The amino acids under study are Aib (α-amino isobutyric acid or α-methyl alanine), Deg (α,α-diethyl glycine), Dpg (α,α-dipropyl glycine), Dibg (α,α-di-isobutyl glycine), Dhg (α,α-dihexyl glycine), DΦg (α,α-diphenyl glycine), Dbzg (α,α-dibenzyl glycine), Ac6c (α,α-cyclohexyl glycine), and Dmg (α,α-dihydroxymethyl glycine). It is hypothesized that these amino acids are able to induce well-defined secondary structure in peptidomimetics.

Modeling of peptaibol analogues incorporating nonpolar α,α-dialkyl glycines shows improved α-helical preorganization and spontaneous membrane permeation.

In this study, we investigate the effect of nine noncanonical α,α-dialkyl glycines on the structure, dynamics, and membrane permeation properties of a small peptaibol, peptaibolin. The noncanonical amino acids under study are Aib (α-amino isobutyric acid), Deg (α,α-diethyl glycine), Dpg (α,α-dipropyl glycine), Dibg (α,α-di-isobutyl glycine), Dhg (α,α-dihexyl glycine), DΦg (α,α-diphenyl glycine), Db(z)g (α,α-dibenzyl glycine), Ac6c (α,α-cyclohexyl glycine), and Dmg (α,α-dihydroxymethyl glycine). It is hypothesized that these amino acids are able to induce well-defined secondary structures in peptidomimetics.