A Machine Learning Approach for Predicting Caco-2 Cell Permeability in Natural Products from the Biodiversity in Peru.

Background: Peru is one of the most biodiverse countries in the world, which is reflected in its wealth of knowledge about medicinal plants. However, there is a lack of information regarding intestinal absorption and the permeability of natural products. The human colon adenocarcinoma cell line (Caco-2) is an in vitro assay used to measure apparent permeability.

Protection against Oxidative Stress and Metabolic Alterations by Synthetic Peptides Derived from Seed Protein.

The ability of multifunctional food-derived peptides to act on different body targets make them promising alternatives in the prevention/management of chronic disorders. The potential of (pajuro) protein as a source of multifunctional peptides was proven. Fourteen selected synthetic peptides identified in an alcalase hydrolyzate from pajuro protein showed in vitro antioxidant, anti-hypertensive, anti-diabetic, and/or anti-obesity effects.

Formation Mechanism of Inter-Crosslink in DNA by Nitrogen Oxides Pollutants through A Diazonium Intermediate.

Outdoor air pollution is a mixture of multiple atmospheric pollutants, among which nitrogen oxide (NOx) stands out due to its association with several diseases. NOx reactivity can conduct to DNA damage as severe as interstrand crosslinks (ICL) formation, that in turn is able to block DNA replication and transcription. Experimental studies have suggested that the ICL formation due to NOx is realized through a diazonium intermediate (DI).

The urokinase plasminogen activator binding to its receptor: a quantum biochemistry description within an in/homogeneous dielectric function framework with application to uPA-uPAR peptide inhibitors.

Despite being recognized as a therapeutic target in the processes of cancer cell proliferation and metastasis for over 50 years, the interaction of the urokinase plasminogen activator uPA with its receptor uPAR still needs an improved understanding. High resolution crystallographic data (PDB ) of the uPA-uPAR binding geometry was used to perform quantum biochemistry computations within the density functional theory (DFT) framework. A divide to conquer methodology considering a mixed homogeneous/inhomogeneous dielectric model and explicitly taking water molecules into account was employed to obtain a large set of uPA-uPAR residue-residue interaction energies.

Phylogenetic, molecular evolution and structural analyses of the WFDC1/prostate stromal protein 20 (ps20).

The WFDC1 gene is frequently down-regulated or lost in prostate cancer, and the encoded protein, ps20, has been implicated in epithelial cell behaviour and angiogenesis. However, ps20 remains largely uncharacterised with respect to its structure and interacting partners. This study characterised the evolution, functionality and structural characteristics of WFDC1/ps20 using phylogenetic reconstruction and other computational approaches.

Explaining urokinase type plasminogen activator inhibition by amino-5-hydroxybenzimidazole and two naphthamidine-based compounds through quantum biochemistry.

Urokinase plasminogen activator (uPA) is a biomarker and therapeutic target for several cancer types whose inhibition has been shown to slow tumor growth and metastasis. In this work, crystallographic data of uPA complexed with distinct ligands (PDB id: 1SQA, 1SQO, and 1FV9) were used to perform quantum biochemistry calculations based on the framework of density functional theory (DFT) and within the molecular fractionation with conjugated caps (MFCC) scheme. Our calculations revealed a total energy interaction of -107.

Human-specific features of the G-quadruplex in the androgen receptor gene promoter: A comparative structural and dynamics study.

The androgen receptor (AR) promoter contains guanine-rich regions that are able to fold into polymorphic G-quadruplex (GQ) structures, and whose deletion decreases AR gene transcription. Our attention was focused on this region because of the frequent termination of sequencing reactions during promoter methylation studies. UV and circular dichroism (CD) spectroscopy of synthetic oligonucleotides encompassing these guanine-rich regions suggested a parallel quadruplex topology with three guanine quartets and three side loops in the three cases.

KLK14 interactions with HAI-1 and HAI-2 serine protease inhibitors: A molecular dynamics and relative free-energy calculations study.

Kallikrein 14 (KLK14) is a serine protease linked to several pathologies including prostate cancer and positively correlates with Gleason score. Though KLK14 functioning in cancer is poorly understood, it has been implicated in HGF/Met signaling, given that KLK14 proteolytically inhibits HGF activator-inhibitor 1 (HAI-1), which strongly inhibits pro-HGF activators, thereby contributing to tumor progression. In this work, KLK14 binding to either hepatocyte growth factor activator inhibitor type-1 (HAI-1) or type-2 (HAI-2) was essayed using homology modeling, molecular dynamic simulations and free-energy calculations through MM/PBSA and MM/GBSA.

Nonenzymatic Reactions above Phospholipid Surfaces of Biological Membranes: Reactivity of Phospholipids and Their Oxidation Derivatives.

Phospholipids play multiple and essential roles in cells, as components of biological membranes. Although phospholipid bilayers provide the supporting matrix and surface for many enzymatic reactions, their inherent reactivity and possible catalytic role have not been highlighted. As other biomolecules, phospholipids are frequent targets of nonenzymatic modifications by reactive substances including oxidants and glycating agents which conduct to the formation of advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs).

Reactivity of a phospholipid monolayer model under periodic boundary conditions: a density functional theory study of the Schiff base formation between phosphatidylethanolamine and acetaldehyde.

A mechanism for the formation of the Schiff base between an acetaldehyde and an amine-phospholipid monolayer model based on Dmol3/density functional theory calculations under periodic boundary conditions was constructed. This is the first time such a system has been modeled to examine its chemical reactivity at this computation level. Each unit cell contains two phospholipid molecules, one acetaldehyde molecule, and nine water molecules.