Active Site Of Protein Research Articles

β-Lactamases Evolve against Antibiotics by Acquiring Large Active-Site Electric Fields.

A compound bound covalently to an enzyme active site can act either as a substrate if the covalent linkage is readily broken up by the enzyme or as an inhibitor if the bond dissociates slowly. We tracked the reactivity of such bonds associated with the rise of the resistance to penicillin G (PenG) in protein evolution from penicillin-binding proteins (PBPs) to TEM β-lactamases and with the development of avibactam (Avb) to overcome the resistance. We found that the ester linkage in PBP-PenG is resistant to hydrolysis mainly due to the small electric fields present in the protein active site. Conversely, the same linkage in the descendant TEM-PenG experiences large electric fields that stabilize the more charge-separated transition state and thus lower the free energy barrier to hydrolysis. Specifically, the electric fields were improved from -59 to -140 MV/cm in an ancient evolution dating back billions of years, contributing 5 orders of magnitude rate acceleration. This trend continues today in the nullification of newly developed antibiotic drugs. The fast linkage hydrolysis acquired from evolution is counteracted by the upgrade of PenG to Avb whose linkage escapes from the hydrolysis by returning to a low-field environment. Using the framework of electrostatic catalysis, the electric field, an observable from vibrational spectroscopy, provides a unifying physical metric to understand protein evolution and to guide the design of covalent drugs.

Using enzymes to tame nitrogen-centred radicals for enantioselective hydroamination.

The formation of C-N bonds-of great importance to the pharmaceutical industry-can be facilitated enzymatically using nucleophilic and nitrene transfer mechanisms. However, neither natural nor engineered enzymes are known to generate and control nitrogen-centred radicals, which serve as valuable species for C-N bond formation. Here we use flavin-dependent 'ene'-reductases with an exogenous photoredox catalyst to selectively generate amidyl radicals within the protein active site. These enzymes are engineered through directed evolution to catalyse 5-exo, 6-endo, 7-endo, 8-endo, and intermolecular hydroamination reactions with high levels of enantioselectivity. Mechanistic studies suggest that radical initiation occurs via an enzyme-gated mechanism, where the protein thermodynamically activates the substrate for reduction by the photocatalyst. Molecular dynamics studies indicate that the enzymes bind substrates using non-canonical binding interactions, which may serve as a handle to further manipulate reactivity. This approach demonstrates the versatility of these enzymes for controlling the reactivity of high-energy radical intermediates and highlights the opportunity for synergistic catalyst strategies to unlock previously inaccessible enzymatic functions.

Engineering enzyme activity using an expanded amino acid alphabet.

Enzyme design and engineering strategies are typically constrained by the limited size of nature's genetic alphabet, comprised of only 20 canonical amino acids. In recent years, site-selective incorporation of non-canonical amino acids (ncAAs) via an expanded genetic code has emerged as a powerful means of inserting new functional components into proteins, with hundreds of structurally diverse ncAAs now available. Here, we highlight how the emergence of an expanded repertoire of amino acids has opened new avenues in enzyme design and engineering. ncAAs have been used to probe complex biological mechanisms, augment enzyme function and, most ambitiously, embed new catalytic mechanisms into protein active sites that would be challenging to access within the constraints of nature's genetic code. We predict that the studies reviewed in this article, along with further advances in genetic code expansion technology, will establish ncAA incorporation as an increasingly important tool for biocatalysis in the coming years.

Conserved Water Networks Identification for Drug Design Using Density Clustering Approaches on Positional and Orientational Data.

This work describes the development and testing of a method for the identification and classification of conserved water molecules and their networks from molecular dynamics (MD) simulations. The conserved waters in the active sites of proteins influence protein-ligand binding. Recently, several groups have argued that a water network formed from conserved waters can be used to interpret the thermodynamic signature of the binding site. We implemented a novel methodology in which we apply the complex approach to categorize water molecules extracted from the MD simulation trajectories using clustering approaches. The main advantage of our methodology as compared to current state of the art approaches is the inclusion of the information on the orientation of hydrogen atoms to further inform the clustering algorithm and to classify the conserved waters into different subtypes depending on how strongly certain orientations are preferred. This information is vital for assessing the stability of water networks. The newly developed approach is described in detail as well as validated against known results from the scientific literature including comparisons with the experimental data on thermolysin, thrombin, and Haemophilus influenzae virulence protein SiaP as well as with the previous computational results on thermolysin. We observed excellent agreement with the literature and were also able to provide additional insights into the orientations of the conserved water molecules, highlighting the key interactions which stabilize them. The source code of our approach, as well as the utility tools used for visualization, are freely available on GitHub.

Sequencing of fosA: A Rapid and Inexpensive Method for Discriminating Klebsiella pneumoniae CC258 from Other Clones.

Typing carbapenem-resistant Klebsiella pneumoniae (CR-KPN) is crucial in controlling their dissemination and solving outbreaks. In this context, we searched for an effective, faster, and cheaper alternative technique to type KPN by analyzing the fosAKP sequence. We analyzed the nucleotide sequences of chromosomal fosAKP gene in 350 KPN genomes (70 per sequence type [ST] or clonal complex [CC]). Assembly genomes were randomly downloaded from NCBI and annotated using RAST in PATRIC platform. The isolate STs were verified using multilocus sequence typing 2.0 by the Center for Genomic Epidemiology. Chromosomally encoded fosAKP was confirmed in MLplasmid, and the sequence alignments were performed in Clustal Omega. The amino acid sequences were analyzed using SNAP2 and SMART platforms. Out of the 70 genomes analyzed for each ST/CC, we observed 100% fosA sequence identity for CC258/11, ST15, ST307, and ST101. For ST16, only two fosA sequences were different from each other. We observed differences in amino acid sequences at positions 25 and 79 (ST16) and 86 (ST16, ST101). The C-terminal (amino acid 138, 139, 140) was different for each cluster. None of these polymorphisms is related to the protein active site. Moreover, L25Q (ST16) polymorphism was predicted to probably affect the protein function. We observed that chromosomal fosAKP sequences from KPN are highly conserved in ST15, ST307, ST16, ST101, and CC258/11, suggesting fosAKP sequencing as an alternative, easier, faster, and less expensive technique in identifying epidemiological STs for KPN, and discriminating them from CC258/11.

Molecular Docking Study of Novel Nitrofuran Derivatives As Urinary Tract Anti Infectives

Modern drug design commonly uses molecular docking to understand drug-receptor interaction. For docking tests against 1YLU, an E. coli nitro-reductase, substituted furan derivatives were used in the current work. The study's primary goal is to dock the chosen nitrofuran derivatives onto the protein and compare the results to those of nitrofurantoin as a standard drug. PyRx and the discovery studio visualizer (DSV) application were used to carry out the molecular docking analysis, and E. coli nitro-reductase (1YLU) was retrieved from the protein data bank (PDB) website. All seven of the nitrofuran compounds docking scores were discovered to range between -5.9 and -8.8 Kcal/mol. Compound 2a received the highest binding score, with a score of -8.80 Kcal/mol.At the protein active site, compound 2a interacts with amino acids such as glutamic acid (GLU 165), arginine (ARG 10 & 207), serine (SER 39 & 12), glutamine (GLN 142), and lysine (LYS205).Numerous nitrofuran substituted compounds have been identified for the activity and the nitrofuran derivatives have been discovered to exhibit urinary tract anti-infective activities.

2,4‐Bis(2‐(E)‐arylidenehydrazinyl)quinazolines: Expeditious Synthesis, Characterization, Antiproliferative Effects against Breast Cancer Cell Line and Molecular Docking Studies

AbstractConsidering the immense significance of molecular hybridization in development of efficacious antiproliferative agents, the present research work demonstrates the expeditious synthesis of twelve electronically different and novel 2,4‐bis(2‐(E)‐arylidenehydrazinyl)quinazolines 4 a–4 l. Their exact molecular structures have been established by careful analysis of spectroscopic (IR, 1H & 13C‐NMR) and HRMS data. Observed results from the MTT assay indicated that all synthesized derivatives 4 a–4 l displayed substantial growth arrest for breast (MCF‐7) cancer cell line. Specifically, 2,4‐bis(2‐(E)‐4‐methoxy benzylidenehydrazinyl)quinazoline (4 a) and 2,4‐bis(2‐(E)‐4‐bromobenzylidenehydrazinyl) quinazoline (4 b) displayed lowest GI50=139.34±7.44 μM and 145.34±2.11 μM respectively, against breast (MCF‐7) cancer cell line. Additionally, molecular docking studies have been performed to investigate the type of favourable interactions of quinazoline bis‐hydrazones with active sites of protein (PDB ID : 4ASD). Computational studies show that derivative 4 a displayed high binding affinity into the ATP binding sites of 4ASD, which support in vitro results obtained in the present study.

IN SILICO EVIDENCE OF THE EFFICACY OF PHYTOCOMPONENTS AS COMPETITIVE INHIBITORS AGAINST A TOBACCO SMOKE CARCINOGEN IN NON-SMALL CELL LUNG CANCER

Cigarette smoke is a major risk factor in the development of Non-small cell lung cancer (NSCLC). Nicotine- derived nitrosamine ketone (NNK) is an important carcinogen present in cigarette smoke that induces tumor metastasis by activation of a protein kinase cascade, including Focal adhesion kinase (FAK). The present investigation was aimed at employing molecular docking studies to establish binding interactions and comparison of phytocomponents from different herbs and selected Rosmarinic acid derivatives against the target protein FAK with the purpose of blocking the binding of Nicotine-derived nitrosamine ketone (NNK). Molegro virtual docker (MMV) and Hex (version 8.0.0) software was used as docking tool for investigating the interaction of the protein active site residues with the phytocomponents. Molegro molecular viewer (MMV) and Biovia Discovery studio 2017 R2 visualizer were used to identify the amino acid interactions between phytocomponents and protein and also to calculate binding scores. The molecular interaction of NNK with the target protein was also done to obtain the binding energy of this carcinogen with the protein. Rosmarinic acid derivatives manifested the highest docking score with the target protein FAK. In comparison, NNK showed weaker binding score with FAK. In addition the derivatives showed common interacting amino acids. Hence, docking studies indicated that phytocomponents and certain derivatives could effectively bind to the same active site of FAK and block its interaction with NNK. Thus, in nicotine exposed NSCLC patients, Rosmarinic acid derivatives may work as effective competitive binders.

LY3041658/ interleukin-8 complex structure as targets for IL-8 small molecule inhibitors discovery using a combination of in silico methods

ABSTRACT Since interleukin-8 (IL-8/CXCL8) and its receptor, CXCR1 and CXCR2, were known in the early 1990s, biological pathways related to these proteins were proven to have high clinical value in cancer and inflammatory/autoimmune conditions treatment. Recently, IL-8 has been identified as biomarker for severe COVID-19 patients and COVID-19 prognosis. Boyles et al. (mAbs 12 (2020), pp. 1831880) have published a high-resolution X-ray crystal structure of the LY3041658 Fab in a complex human CXCL8. They described the ability to bind to IL-8 and the blocking of IL-8/its receptors interaction by the LY3041658 monoclonal antibody. Therefore, the study has been designed to identify potential small molecules inhibiting interleukin-8 by targeting LY3041658/IL-8 complex structure using an in silico approach. A structure‑based pharmacophore and molecular docking models of the protein active site cavity were generated to identify possible candidates, followed by virtual screening with the ZINC database. ADME analysis of hit compounds was also conducted. Molecular dynamics simulations were then performed to survey the behaviour and stability of the ligand-protein complexes. Furthermore, the MM/PBSA technique has been utilized to evaluate the free binding energy. The final data confirmed that one newly obtained compound, ZINC21882765, may serve as the best potential inhibitor for IL-8.

Antioxidant, Antibacterial, Antidiabetic Potential, and In silico Analysis of Rhus chinensis from Western Nepal.

Rhus chinensis Mill, indigenous wild fruit primarily found in the hilly region of Nepal. The ripe fruit is very sour and considered medicinal as a remedy for colic pain. In addition, their astringent and styptic qualities are used internally to treat illnesses such as diarrhea and hemorrhage. Also, they are used as a common component of polyherbal medications for diabetic mellitus. This work aimed to determine the total phenolic and flavonoid content, antioxidant, antibacterial, α-glucosidase, and α-amylase inhibition activity of the crude extract and fractions of Rhus chinensis Mill. Additionally, molecular docking of compounds from Rhus chinensis was performed. Folin Ciocalteu's (FC) reagent was used to estimate total phenolic content. Likewise, the aluminium trichloride method was applied to determine total flavonoid content. A 2,2-diphenyl-1- picrylhydrazyl (DPPH) free radical scavenging assay was performed for the antioxidant activity. Furthermore, the substrate-based enzyme inhibition assay was carried out for α-glucosidase and α- amylase inhibition activity of R. chinensis. P-nitrophenyl-α-D-glucopyranoside (PNPG) and 2- Chloro-4-Nitrophenyl-α-D-Maltotrioside (CNPG3) were used as substrates for α-glucosidase and α- amylase inhibition assay, respectively. Similarly, the well-diffusion method was used for the antibacterial activity. Autodock vina was used to perform molecular docking. The total phenolic and flavonoid content of R. chinensis fruit were 117.092±1.1 mg GAE/g and 62.41±1.23 mg QE/g, respectively. The IC50 value for antioxidant activity of the crude extract and its fractions ranged from 3.12±1.15μg/mL to 50.85±2.10μg/mL. Similarly, the IC50 for α- glucosidase inhibition ranged from2.33±1.01μg/mL to 28.34±2.79μg/mL. Likewise, The IC50 of R. chinensis crude methanolic extract against α-amylase was 120.3±1.382μg/mL. The antibacterial activity of R. chinensis was effective against gram-positive bacteria; Staphylococcus aureus (ZOI=11.0) and Bacillus subtilis (ZOI=9.0). Quercetin-3-O-rhamnoside and Myricetin-3-Orhamnoside showed excellent binding to the active site of protein with binding energy -9.4kcal/mol and -9.6kcal/mol, respectively. Rhus chinensis Mill is a potent antioxidant and inhibits enzymes; α-glucosidase and α- amylase. In addition, the methanolic extract of this plant shows antibacterial activity. However, further research is required to determine the inhibiting compounds.

Development of pyrrolidine and isoindoline derivatives as new DPP8 inhibitors using a combination of 3D-QSAR technique, pharmacophore modeling, docking studies, and molecular dynamics simulations

ABSTRACT Dipeptidyl peptidase proteins (DPPs) are a family of serine proteases with an active, vital role in multiple pathological conditions, including different types of cancer and autoimmune diseases. DPP inhibitors can induce an inflammatory form of cell death by activating inflammasome sensors and pro-caspase 1. This study used docking calculations and extended molecular dynamics simulations to investigate the interaction patterns for DPP8-inhibitor complex structures. We also implemented a novel procedure to develop new DPP8 inhibitors using pharmacophore and CoMFA models, docking studies, and molecular dynamics simulations. Our results showed the critical role of Glu 275, Glu 276, and Tyr 788 residues in the active site of protein in DPP8-inhibitor interaction. We also provided a platform for comparing the effectiveness of the most important DPP8 inhibitors. Moreover, we introduced a new 1G244 derivative with the highest affinity among all the studied compounds to inhibit DPP8 protein.

A designed photoenzyme for enantioselective [2+2] cycloadditions.

The ability to program new modes of catalysis into proteins would allow the development of enzyme families with functions beyond those found in nature. To this end, genetic code expansion methodology holds particular promise, as it allows the site-selective introduction of new functional elements into proteins as noncanonical amino acid side chains1-4. Here we exploit an expanded genetic code to develop a photoenzyme that operates by means of triplet energy transfer (EnT) catalysis, a versatile mode of reactivity in organic synthesis that is not accessible to biocatalysis at present5-12. Installation of a genetically encoded photosensitizer into the beta-propeller scaffold of DA_20_00 (ref. 13) converts a de novo Diels-Alderase into a photoenzyme for [2+2] cycloadditions (EnT1.0). Subsequent development and implementation of a platform for photoenzyme evolution afforded an efficient and enantioselective enzyme (EnT1.3, up to 99% enantiomeric excess (e.e.)) that can promote intramolecular and bimolecular cycloadditions, including transformations that have proved challenging to achieve selectively with small-molecule catalysts. EnT1.3 performs >300 turnovers and, in contrast to small-molecule photocatalysts, can operate effectively under aerobic conditions and at ambient temperatures. An X-ray crystal structure of an EnT1.3-product complex shows how multiple functional components work in synergy to promote efficient and selective photocatalysis. This study opens up a wealth of new excited-state chemistry in protein active sites and establishes the framework for developing a new generation of enantioselective photocatalysts.

Identification of novel inhibitors of Neisseria gonorrhoeae MurI using homology modeling, structure-based pharmacophore, molecular docking, and molecular dynamics simulation-based approach

MurI is one of the most significant role players in the biosynthesis of the peptidoglycan layer in Neisseria gonorrhoeae (Ng). We attempted to highlight the structural and functional relationship between Ng-MurI and D-glutamate to design novel molecules targeting this interaction. The three-dimensional (3D) model of the protein was constructed by homology modeling and the quality and consistency of generated model were assessed. The binding site of the protein was identified by molecular docking studies and a pharmacophore was identified using the interactions of the control ligand. The structure-based pharmacophore model was validated and employed for high-throughput virtual screening and molecular docking to identify novel Ng-MurI inhibitors. Finally, the model was optimized by molecular dynamics (MD) simulations and the optimized model complex with the substrate glutamate and novel molecules facilitated us to confirm the stability of the protein-ligand docked complexes. The 100 ns MD simulations of the potential lead compounds with protein confirmed that the modeled complexes were stable. This study identifies novel potential compounds with good fitness and docking scores, which made the interactions of biological significance within the protein active site. Hence, the identified compounds may act as new leads to design and develop Ng-MurI inhibitors. Communicated by Ramaswamy H. Sarma

Staphylococcus aureus Exfoliative Toxin E, Oligomeric State and Flip of P186: Implications for Its Action Mechanism.

Staphylococcal exfoliative toxins (ETs) are glutamyl endopeptidases that specifically cleave the Glu381-Gly382 bond in the ectodomains of desmoglein 1 (Dsg1) via complex action mechanisms. To date, four ETs have been identified in different Staphylococcus aureus strains and ETE is the most recently characterized. The unusual properties of ETs have been attributed to a unique structural feature, i.e., the 180° flip of the carbonyl oxygen (O) of the nonconserved residue 192/186 (ETA/ETE numbering), not conducive to the oxyanion hole formation. We report the crystal structure of ETE determined at 1.61 Å resolution, in which P186(O) adopts two conformations displaying a 180° rotation. This finding, together with free energy calculations, supports the existence of a dynamic transition between the conformations under the tested conditions. Moreover, enzymatic assays showed no significant differences in the esterolytic efficiency of ETE and ETE/P186G, a mutant predicted to possess a functional oxyanion hole, thus downplaying the influence of the flip on the activity. Finally, we observed the formation of ETE homodimers in solution and the predicted homodimeric structure revealed the participation of a characteristic nonconserved loop in the interface and the partial occlusion of the protein active site, suggesting that monomerization is required for enzymatic activity.

Photochemical and Molecular Dynamics Studies of Halide Binding in Flavoenzyme Glucose Oxidase.

Glucose oxidase (GOX), a characteristic flavoprotein oxidase with widespread industrial applications, binds fluoride (F- ) and chloride (Cl- ). We investigated binding properties of halide inhibitors of GOX through time-resolved spectral characterization of flavin-related photochemical processes and molecular dynamic simulations. Cl- and F- bind differently to the protein active site and have substantial but opposite effects on the population and decay of the flavin excited state. Cl- binds closer to the flavin, whose excited-state decays in <100 fs due to anion-π interactions. Such interactions appear absent in F- binding, which, however, significantly increases the active-site rigidity leading to more homogeneous, picosecond fluorescence decay kinetics. These findings are discussed in relation to the mechanism of halide inhibition of GOX by occupying the accommodation site of catalytic intermediates and increasing the active-site rigidity.

Essential oil from Oliveria decumbens accelerates in vivo wound healing: a possible mechanism by the involvement of glycogen synthase kinase-3

Background and objective: The development of new products for skin care and wound treatment is continuous, and herbal medicine plays an important role in the treatments. Oliveria decumbens, a plant from the family Apiaceae, has been reported to enclose many pharmacological properties. This study aimed to detect the effect of the essential oil of Oliveria decumbens as an antibacterial and wound healing agent. Methods: The antibacterial properties of Oliveria decumbens were studied by the disk diffusion method. In addition, the excision model of wound healing was applied to rats, and the AutoDock method was used to study the mechanism of action. Results: The essential oil extracted from Oliveria decumbens showed antibacterial activities against gram-positive and gram-negative bacteria, and the wound healing effect was comparable to the standard skin cream. Thymol was predicted to be the strongest binder of GSK-3 protein active site forming the most stable complex with hydrogen bond and hydrophobic interaction. The second-best binders were P-Cymene, Limonene, Gamma-Terpinene, and Carvacrol. Conclusion: The observed data backed the original claim of antibacterial and wound healing properties of Oliveria decumbens extracted essential oil. Keywords: Oliveria decumbens; Wound healing; Disk diffusion; AutoDock Vina method.

Anti-lung cancer drug discovery approaches by polysaccharides: an in silico study, quantum calculation and molecular dynamics study

Lung cancer (LC) is one of the major and risky health defects even the serious cause for death in concurrent era. But no potential drugs even chemotherapeutic agents have been discovered with approval of health safety although some non-toxic biological macromolecules, such as polysaccharides and polysaccharide–protein complexes, have obtained as anti-lung cancer properties. This study conveys the anti-lung cancer properties of 45 polysaccharide derivatives collected from PubChem database. Primarily, the PASS prediction was performed to depict their anti-cancer activity, and 37 compounds showed the desired results. Next, the chemical descriptors, such as HOMO, LUMO, softness, and hardness etc, were calculated through the density functional theory (DFT) for quantum properties. Secondly, the auto molecular docking was executed to delineate the protein-ligand interactions, binding ability and inhibition of active sites of proteins. Additionally, the compounds showed docking score more than −6.40 kcal/mol, and the highest binding affinity was at −10.00 kcal/mol even 15 compounds have higher binding score (-8.6 to −10.0) than approved drugs, Gemcitabine. Succeeding, the most common protein residue, VAL 647, was blocked by ligands for the main protein (1X2J). In addition, five protein’s active sites were determined to make the relative study of protein-ligand interactions. As a result, the target docking against five proteins was performed, and it was found that the targeted docking score as the binding affinity is lower than auto docking. Finally, a comparative study between auto docking and targeted docking was performed for the most common five lung cancer proteins founded in three organisms. Communicated by Ramaswamy H. Sarma

Z. officinale-doped silver/calcium oxide nanocomposites: Catalytic activity and antimicrobial potential with molecular docking analysis

In this study, green synthesized Ag/CaO combined with a reducing agent based on a plant extract was synthesized. Then, the catalytic and antimicrobial potential of extract doped-Ag/CaO was investigated. Bio-reducing synthesis protocol was followed to fabricate Ag/CaO nanocomposites (NCs) by reducing and capping with Zingiber officinale. A series of characterization techniques was employed to examine structural, morphological and optical properties of Ag/CaO. The experimental findings favored doped nanocomposites for use as effective catalysts that degraded toxic dyes such as methylene blue and ciprofloxacin and exhibited strong antimicrobial activity against Escherichia coli (E. coli), and Staphylococcus aureus (S. aueus). Furthermore, a molecular docking investigation determined binding interaction patterns between NCs and targeted cell protein active sites. The obtained results suggested green synthesized Ag/CaO as the most effective inhibitor of dihydrofolate reductase, DNA gyrase, and FabB enzymes. Findings revealed highly economical, non-toxic, and readily available Z. officinale rhizome extract as a potential capping agent to fabricate Ag/CaO for potential applications to reduce major economic losses in the dairy industry for the first time in Pakistan.

Solvent Sites Improve Docking Performance of Protein-Protein Complexes and Protein-Protein Interface-Targeted Drugs.

Protein-protein interactions (PPIs) are essential, and modulating their function through PPI-targeted drugs is an important research field. PPI sites are shallow protein surfaces readily accessible to the solvent, thus lacking a proper pocket to fit a drug, while their lack of endogenous ligands prevents drug design by chemical similarity. The development of PPI-blocking compounds is, therefore, a tough challenge. Mixed solvent molecular dynamics has been shown to reveal protein-ligand interaction hot spots in protein active sites by identifying solvent sites (SSs). Furthermore, our group has shown that SSs significantly improve protein-ligand docking. In the present work, we extend our analysis to PPI sites. In particular, we analyzed water, ethanol, and phenol-derived sites in terms of their capacity to predict protein-drug and protein-protein interactions. Subsequently, we show how this information can be incorporated to improve both protein-ligand and protein-protein docking. Finally, we highlight the presence of aromatic clusters as key elements of the corresponding interactions.

Quantum tunneling of three-spine solitons through excentric barriers

Macromolecular protein complexes catalyze essential physiological processes that sustain life. Various interactions between protein subunits could increase the effective mass of certain peptide groups, thereby compartmentalizing protein α-helices. Here, we study the differential effects of applied massive barriers upon the soliton-assisted energy transport within proteins. We demonstrate that excentric barriers, localized onto a single spine in the protein α-helix, reflect or trap three-spine solitons as effectively as concentric barriers with comparable total mass. Furthermore, wider protein solitons, whose energy is lower, require heavier massive barriers for soliton reflection or trapping. Regulation of energy transport, delivery and utilization at protein active sites could thus be achieved through control of the soliton width, or of the effective mass of the protein subunits.