Molecular mechanics/Poisson–Boltzmann (Generalized-Born) surface area is one of the most popular methods to estimate binding free energies. This method has been proven balance accuracy and computational efficiency, especially when dealing with large systems. As a result its popularity, several programs have developed for performing MM/PB(GB)SA calculations within GROMACS community. These programs, however, present limitations. Here we gmx_MMPBSA, new tool perform end-state energy from...

Abstract AMDock (Assisted Molecular Docking) is a user-friendly graphical tool to assist in the docking of protein-ligand complexes using Autodock Vina and AutoDock4, including option Autodock4Zn force field for metalloproteins. integrates several external programs (Open Babel, PDB2PQR, AutoLigand, ADT scripts) accurately prepare input structure files optimally define search space, offering alternatives different degrees user supervision. For visualization molecular structures, uses PyMOL,...

We present NbThermo-a first-in-class database that collects melting temperatures (Tm), amino acid sequences and several other categories of useful data for hundreds nanobodies (Nbs), compiled from an extensive literature search. This so-far unique currently contains up-to-date, manually curated 564 Nbs. It represents a contribution to efforts aimed at developing new algorithms reliable Tm prediction assist Nb engineering wide range applications these biomolecules. Nbs the two most common...

The number of applications for nanobodies is steadily expanding, positioning these molecules as fast-growing biologic products in the biotechnology market. Several their require protein engineering, which turn would greatly benefit from having a reliable structural model nanobody interest. However, with antibodies, modeling still challenge. With rise artificial intelligence (AI), several methods have been developed recent years that attempt to solve problem modeling. In this study, we...

To design and construct a new synthetic nanobody library using structure-based approach that seeks to maintain high protein stability increase the number of functional variants within combinatorial space mutations.Synthetic (Nb) libraries are emerging as an attractive alternative animal immunization for selection stable, affinity Nbs. Two key features define Nb library: framework CDR design. We selected universal VHH from cAbBCII10 Nb. CDR1 CDR2 were designed with same fixed length in...

Computational alanine scanning with the molecular mechanics generalized Born surface area (MM/GBSA) method constitutes a widely used approach for identifying critical residues at protein–protein interfaces. Despite its popularity, MM/GBSA still has certain drawbacks due to dependence on many factors. Here, we performed systematical study impact of four different parameters, namely, internal dielectric constant, model, entropic term, and inclusion structural waters accuracy computational...

Our work is composed of a python program for programmatic data mining PubChem to collect implement machine learning-based AutoQSAR algorithm generate drug leads the flaviviruses—Dengue and West Nile. The generated by are fed as inputs AutoDock Vina package automated in silico modelling interaction between compounds chosen Dengue Nile target methyltransferase, whose inhibition control viral replication. involves feature selection, QSAR modelling, validation prediction. generated, each time...

Invasive fungal infections represent a public health problem that worsens over the years with increasing resistance to current antimycotic agents. Therefore, there is compelling medical need of widening antifungal drug repertoire, following different methods such as repositioning, identification and validation new molecular targets developing inhibitors against these targets. In this work we developed structure-based strategy for repositioning design, which can be applied infectious fungi...

The number of applications for nanobodies is steadily expanding, positioning these molecules as fast-growing biologic products in the biotechnology market. Several their require protein engineering, which turn would greatly benefit from having a reliable structural model nanobody interest. However, with antibodies, modeling still challenge. With rise artificial intelligence (AI), several methods have been developed recent years that attempt to solve problem modeling. In this study, we...

Vps34 is the only isoform of PI3K family in fungi, making this protein an attractive target to develop new treatments against pathogenic fungi. The high structural similarity between active sites human and fungal makes repurposing inhibitors appealing strategy. Nonetheless, while some cross-reactive might have potential treat infections, a safer approach prevent undesired side effects would be identify molecules that specifically inhibit Vps34. This study presents parameterization four LIE...

In healthcare there is a pursuit for employing interpretable algorithms to assist professionals in several decision scenarios. Following the Predictive, Descriptive and Relevant (PDR) framework, definition of machine learning as machine-learning model that explicitly simple frame determines relationships either contained data or learned by are relevant its functioning categorization models post-hoc, acquiring interpretability after training, model-based, being intrinsically embedded...

The work is composed of python based programmatic tool that automates the dry lab drug discovery workflow for coronavirus. Firstly, program written to automate process data mining PubChem database collect required perform a machine learning AutoQSAR algorithm through which leads coronavirus are generated. acquisition from was carried out web scrapping techniques. involves feature and descriptor selection, QSAR modelling, validation prediction. generated by satisfy Lipinski’s likeness...

<p>The work is composed of python based programmatic tool that automates the dry lab drug discovery workflow for coronavirus. Firstly, program written to automate process data mining PubChem database collect required perform a machine learning AutoQSAR algorithm through which leads coronavirus are generated. The acquisition from was carried out web scrapping techniques. involves feature and descriptor selection, QSAR modelling, validation prediction. generated by satisfy Lipinski’s...

The work is composed of python based programmatic tool that automates the workflow drug discovery for coronavirus. Firstly, program written to automate process data mining PubChem database collect required perform a machine learning AutoQSAR algorithm through which leads coronavirus are generated. acquisition from was carried out web scrapping techniques. involves feature and descriptor selection, QSAR modelling, validation prediction. generated by satisfy Lipinski’s likeness criteria as...

The calculation of absolute binding affinities for protein-inhibitor complexes remains as one the main challenges in computational structure-based ligand design. present work explored calculations surface fractal dimension (as a measure roughness) and relationship with experimental free energies Plasmepsin II complexes. is an attractive target novel therapeutic compounds to treat malaria. However, structural flexibility this enzyme drawback when searching specific inhibitors. Concerning...

Abstract Our work is composed of a python program for programmatic data mining PubChem to collect implement machine learning based AutoQSAR algorithm generate drug leads the flaviviruses – Dengue and West Nile. The generated by are feed as inputs AutoDock Vina package automated In Silico modelling interaction between compounds chosen Nile target methyltransferase, whose inhibition control viral replication. involves feature selection, QSAR modelling, validation prediction. each time run...

Abstract Background Invasive fungal infections account for a high burden of morbidity and mortality. This is aggravated because the toxicity resistance problems associated to current antifungal drugs, which in whole target only handful molecules. In this scenario, new identification drug design, together with repurposing, represent promising strategies. Methods We aim identify test vitro potential therapeutic targets fungi. Our strategy consists identifying proteins active sites (meaning set...