Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge management, analysis interpretation of data in natural products research. Currently, reliance on a disparate set non-standardized, insular, specialized databases presents series challenges for access, both within the discipline integration interoperability between related fields. The fundamental elements exchange are referenced structure-organism pairs that establish relationships distinct molecular...

For a series of different proteins, including structural protein, enzyme, inhibitor, protein marker, and charge-transfer system, we have quantified the higher affinity Na + over K to surface by means molecular dynamics simulations conductivity measurements. Both approaches show that sodium binds at least twice as strongly than potassium does with this effect being present in all proteins under study. Different parts exterior are responsible varying degree for sodium, charged carboxylic...

Virtual screening is becoming an important tool for drug discovery. However, the application of virtual has been limited by lack accurate scoring functions. Here, we present a novel function, MedusaScore, evaluating protein−ligand binding. MedusaScore based on models physical interactions that include van der Waals, solvation, and hydrogen bonding energies. To ensure best transferability do not use any experimental data parameter training. We then test docking decoy recognition binding...

We investigated the potential-energy surface (PES) of phenylalanyl-glycyl-glycine tripeptide in gas phase by means IR/UV double-resonance spectroscopy, and quantum chemical statistical thermodynamic calculations. Experimentally, we observed four conformational structures recorded their IR spectra spectral region 3000-4000 cm(-1). Computationally, PES a combination molecular dynamics/quenching procedures with high-level correlated ab initio found that neither empirical potentials nor various...

Our previous benchmark CCSD(T)/ complete basis set limit calculations were collected into a database named begdb - Benchmark Energy and Geometry DataBase. Web-based interface to this was prepared is available at www.begdb.com. Users can browse, search plot the data online or download structures energy tables.

The formation of a hydrophobic core globular proteins is believed to be the consequence exterior forces entropic nature. This, together with low occurrence hydrogen bonds in protein core, leads opinion that energy contribution folding and stability negligible. We show stabilization inside small protein, rubredoxin, determined by means high-level correlated ab initio calculations (complete basis set limit MP2 + CCSD(T) correction term), amounted ∼50 kcal/mol. These results clearly demonstrate...

The interaction of the water molecule with benzene, polycyclic aromatic hydrocarbons, graphene, and graphite is investigated at density-functional/coupled-cluster (DFT/CC) level theory. accuracy DFT/CC method first demonstrated by a comparison various energies on potential energy surface water−benzene, water−naphthalene, water−anthracene complexes data calculated coupled-cluster basis set limit. water−graphene water−graphite relatively flat diffusion barriers about 1 kJ/mol. structure both...

Interactions between amino acid side chains play a crucial role both within folded protein and the interacting molecules. Here we have selected representative set of 24 400 (20 × 20) possible chain pairs based on data from Atlas Protein Side-Chain Interactions. For each pair, obtained its most favorable interaction geometry structural computed energy in gas phase using several different, commonly used, ab initio force field methods, namely Møller−Plesset perturbation theory (MP2), density...

The protein sequences found in nature represent a tiny fraction of the potential that could be constructed from 20-amino-acid alphabet. To help define properties shaped proteins to stand out space possible alternatives, we conducted systematic computational and experimental exploration random (unevolved) comparison with biological proteins. In our study, combinations secondary structure, disorder, aggregation predictions are accompanied by characterization selected We overall structure...

Proline–tryptophan complexes derived from experimental structures are investigated by quantum chemical procedures known to properly describe the London dispersion energy. We study two geometrical arrangements: “L-shaped”, stabilized an H-bond, and “stacked-like”, where residues in parallel orientation without any H-bond. Interestingly, interaction energies both cases comparable very large (∼7 kcal mol−1). The strength of stabilization stacked arrangement is rather surprising considering fact...

Using a combination of experimental techniques (circular dichroism, differential scanning calorimetry, and NMR) molecular dynamics simulations, we performed an extensive study denaturation the Trp-cage miniprotein by urea guanidinium. The experiments, despite their different sensitivities to various aspects process, consistently point simple, two-state unfolding process. Microsecond simulations with femtosecond time resolution allow us unravel detailed mechanism unfolding. process starts...

Large biomolecules-proteins and nucleic acids-are composed of building blocks which define their identity, properties binding capabilities. In order to shed light on the energetic side interactions amino acids between themselves with deoxyribonucleotides, we present Amino Acid Interaction web server (http://bioinfo.uochb.cas.cz/INTAA/). INTAA offers calculation residue Energy Matrix for any protein structure (deposited in Protein Data Bank or submitted by user) a comprehensive analysis...

Abstract Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge management, analysis interpretation of data in natural products research. Currently, reliance on a disparate set non-standardized, insular, specialized databases presents series challenges for access, both within the discipline integration interoperability between related fields. The fundamental elements exchange are referenced structure-organism pairs that establish relationships distinct...

The evolution of proteins is primarily driven by the combinatorial assembly a limited set pre-existing modules known as protein domains. This modular architecture not only supports diversity natural but also provides robust strategy for engineering, enabling design artificial with enhanced or novel functions various industrial applications. Among these functions, oligomerization plays crucial role in enhancing activity, such increasing binding capacity antibodies. To investigate potential...

In this work we investigate the performance of DFT method, augmented with an empirical dispersion function (DFT-D), paired PCM implicit solvation model, for computation noncovalent interaction energies biologically-relevant, solvated model complexes. It is found that method describes intermolecular interactions within water and ether (protein-like) environments roughly same accuracy as in gas phase. Another important finding that, when environmental effects are taken into account, term...

There is a need for fast, accurate, and reliable method of sampling the conformational space peptides proteins in order to obtain balanced free-energy profile which can lead our understanding protein structure. We have utilized metadynamics study solvated alanine dipeptide molecule, results show that has proven be competent as robust, conformation calculations an explicit solvent, surpassing traditional methods such umbrella sampling. also addressed issue influence different water models on...

Pairing of guanidinium moieties in water is explored by molecular dynamics simulations short arginine-rich peptides and ab initio calculations a pair ions clusters increasing size. Molecular show that, an aqueous environment, the diarginine like-charged ion pairing sterically hindered, whereas Arg-Ala-Arg tripeptide, this significant. This result supported survey protein structure databases, where it found that stacked arginine pairs dipeptide fragments exist solely as being imposed...

Effective simulations of proteins, their complexes, and other amino-acid polymers such as peptides or peptoids are critically dependent on the performance simulation methods ability to map conformational space molecule in question. The most important step this process is choice coordinates which sampling will be executed uniqueness regarding capability unambiguously determine energy minimum free-energy hypersurface. In presented study, we show that metadynamics chosen collective...

The sesquiterpenoid juvenile hormone (JH) is vital to insect development and reproduction. Intracellular JH receptors have recently been established as basic helix-loop-helix transcription factor (bHLH)/PAS proteins in Drosophila melanogaster known germ cell–expressed (Gce) its duplicate paralog, methoprene-tolerant (Met). Upon binding JH, Gce/Met activates target genes. Insects possess multiple native homologs whose molecular activities remain unexplored, diverse synthetic compounds...

Background Blood flukes of the genus Schistosoma cause schistosomiasis, a parasitic disease that infects over 240 million people worldwide, and for which there is need to identify new targets chemotherapeutic interventions. Our research focused on mansoni prolyl oligopeptidase (SmPOP) from serine peptidase family S9, has not been investigated in detail trematodes. Methodology/Principal Findings We demonstrate SmPOP expressed adult worms schistosomula an enzymatically active form. By...

The earliest proteins had to rely on amino acids available early Earth before the biosynthetic pathways for more complex evolved. In extant proteins, a significant fraction of ‘late’ (such as Arg, Lys, His, Cys, Trp and Tyr) belong essential catalytic structure-stabilizing residues. How (or if) could sustain an biosphere has been major puzzle. Here, we analysed two combinatorial protein libraries representing proxies sequence space at different evolutionary stages. first is composed entire...