Predicting the binding affinity of peptides able to interact with major histocompatibility complex (MHC) molecules is a priority for researchers working in identification novel vaccines candidates. Most available approaches are based on analysis sequence known experimental affinity. However, MHC class II receptors, these not very accurate, due intrinsic flexibility complex. To overcome limitations, we propose estimate bound an by averaging score configurations from finite-temperature...

ABSTRACT We present PepFuNN, a new open‐source version of the PepFun package with functions to study chemical space peptide libraries and perform structure–activity relationship analyses. PepFuNN is Python comprising five modules peptides natural amino acids and, in some cases, sequences non‐natural based on availability public monomer dictionary. The allow calculating physicochemical properties, performing similarity analysis using different representations, clustering molecular...

Bioactive peptides are an important class of natural products with great functional diversity. Chemical modifications can improve their pharmacology, yet structural diversity presents unique challenges for computational modeling. Furthermore, data canonical (non-modified) is more abundant than non-canonical (chemically modified). We explored whether current methods sufficient to generalize from datasets. To do this, we first considered two critical aspects the modeling problem, namely choice...

Quinones are secondary metabolites of higher plants associated with many biological activities, including antiviral effects and cytotoxicity. In this study, the anti-herpetic anti-dengue evaluation 27 terpenyl-1,4-naphthoquinone (NQ), 1,4-anthraquinone (AQ) heterocycle-fused quinone (HetQ) derivatives was done in vitro against Human Herpesvirus (HHV) type 1 2, Dengue virus serotype 2 (DENV-2). The cytotoxicity on HeLa Jurkat tumor cell lines also tested. Using plaque forming unit assays,...

Epitopes that bind simultaneously to all human alleles of Major Histocompatibility Complex class II (MHC II) are considered one the key factors for development improved vaccines and cancer immunotherapies. To engineer MHC multiple-allele binders, we developed a protocol called PanMHC-PARCE, based on unsupervised optimization epitope sequence by single-point mutations, parallel explicit-solvent molecular dynamics simulations scoring II-epitope complexes. The idea is accepting mutations not...

Tubulin is a well-validated target for herbicides, fungicides, anti-parasitic, and anti-tumor drugs. Many of the non-cancer tubulin drugs bind to its colchicine site but no colchicine-site anticancer drug available. The composed three interconnected sub-pockets that fit their ligands modify others' preference, making design molecular hybrids (that more than one sub-pocket) difficult task. Taking advantage eighty published X-ray structures in complex with bound site, we generated an ensemble...

Peptide research has increased during the last years due to their applications as biomarkers, therapeutic alternatives or antigenic sub-units in vaccines. The implementation of computational resources have facilitated identification novel sequences, prediction properties, and modelling structures. However, there is still a lack open source protocols that enable straightforward analysis. Here, we present PepFun, compilation bioinformatics cheminformatics functionalities are easy implement...

Age-related macular degeneration (AMD) is an incurable disease associated with aging that destroys sharp and central vision. Increasing evidence implicates both systemic local inflammation in the pathogenesis of AMD. Intravitreal injection anti-vascular endothelial growth factor (VEGF) agents currently first-line therapy for choroidal neovascularization AMD patients. However, a high number patients do not show satisfactory responses to anti-VEGF treatment after three injections. Predictive...

Abstract Summary: myChEMBL is a completely open platform, which combines public domain bioactivity data with source database and cheminformatics technologies. consists of Linux (Ubuntu) Virtual Machine featuring PostgreSQL schema the latest version ChEMBL database, as well RDKit libraries. In addition, self-contained web interface available, can be modified improved according to user specifications. Availability implementation: The VM available at:...

Single-point mutation protocols based on backbone-dependent rotamer libraries show the best performance in predicting equilibrium configurations from molecular dynamics simulations.

The Cry11 family belongs to a large group of -endotoxins that share three distinct structural domains. Among the dipteran-active toxins referred as three-domain toxins, Cry11Aa protein from Bacillus thuringiensis subsp. israelensis (Bti) has been most extensively studied. Despite potential Bti an effective biological control agent, understanding remains incomplete. In this study, five variants obtained via DNA shuffling displayed toxic activity against Aedes aegypti and Culex...

We present an easy, human-readable line notation to describe even complex peptides.

Abstract We present pyPept, a set of executables and underlying python-language classes to easily create, manipulate, analyze peptide molecules using the FASTA, HELM, or recently-developed BILN notations. The framework enables analysis both pure proteinogenic peptides as well those with non-natural amino acids, including support assemble customizable monomer library, without requiring programming. From line notations, is transformed into molecular graph for 2D depiction tasks, calculation...

MyChEMBL is an open virtual platform which provides a free, secure, standardised and easy to use chemoinformatics environment for bioactivity data mining, machine learning, application development, learning teaching. The main technical features of myChEMBL along with its applications future plans are discussed here.

Leishmaniasis is one of the world's most neglected diseases caused by at least 20 different species protozoan parasite Leishmania. Although new drugs have become recently available, current therapy for leishmaniasis still unsatisfactory. A subgroup serine/threonine protein kinases named as related to and C (RAC), or kinase B (PKB)/AKT, has been identified in several organisms including Trypanosoma cruzi parasites. PKB/AKT plays a critical role mammalian cell signaling promoting survival...

Abstract Background Proteases are key drivers in many biological processes, part due to their specificity towards substrates. However, depending on the family and molecular function, they can also display substrate promiscuity which be essential. Databases compiling matrices derived from experimental assays have provided valuable insights into protease recognition. Despite this, there still gaps our knowledge of structural determinants. Here, we compile a set crystal structures with bound...

The Akt-like kinase of Leishmania spp. is a cytoplasmic orthologous protein the serine/threonine B-PKB/human-Akt group, which involved in cellular survival these parasites. By application computational strategy we obtained two specific inhibitors L. panamensis (UBMC1 and UBMC4), are predicted to bind specifically pleckstrin domain (PH) enzyme. We show that phospho-activated parasites under nutritional thermic stress, this phosphorylation blocked by UBMC1 UMBC2 such inhibition leads cell...

In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment of various diseases. Sterculic acid (SA) is cyclopropene fatty with numerous biological activities, generally attributed Stearoyl-CoA desaturase (SCD) inhibitory properties. Additional effects exerted by SA, independently SCD inhibition, may be mediating anti-inflammatory protective roles retinal diseases such age-related macular degeneration...

We present an assessment of different approaches to predict peptide structures using modeling tools. Several small molecule, protein, and peptide-focused methodologies were used for the fast prediction conformers peptides shorter than 30 amino acids. assessed effect including restraints based on annotated or predicted secondary structure motifs. A number in bound conformations solution collected compare In addition, we studied impact changing single acids non-natural residues molecular...

Proteins associated to the PI3K/AKT/mTOR signaling pathway are widely used targets for cancer treatment, and in recent years they have also been evaluated as putative trypanosomatids parasites, such Trypanosoma cruzi. Here, we performed a virtual screening approach find candidates that can bind regions on or near Pleckstrin homology domain of an AKT-like protein T. The compounds were vitro. silico experimental results allowed us identify set potentially alter intracellular through kinase...