Computational analysis of non-covalent interactions in phycocyanin subunit interfaces

Phycocyanins (C-phycocyanin and allophycocyanin) are stable water-soluble trimers (αβ)3 or hexamers (αβ)6, containing dark-blue covalently attached phycocyanobilin chromophore with variety of pharmacological properties. Molecular forces (non-covalent interactions) responsible for the observed differences in thermal and chemical stability of different phycocyanin complexes are not completely understood 1. In this study, we used the manually curated non-redundant dataset of 118 interfaces from 20 X-ray phycocyanin structures (PDB ID codes: 1all, 1b33, 1kn1, 2vjt, 3dbj, 4f0u, 4po5,4rmp, 1cpc, 1gh0, 1f99, 1jbo, 1phn, 2bv8, 2vml, 3o18, 4l1e, 4lm6, 4lms, 4yjj) to gain additional insight to this phenomenon using a robust inter-atomic non-covalent interaction analyzing tool PPCheck (http://caps.ncbs.res.in/ppcheck). For our dataset, the mean interface area was 1088 Å2 and there were on average 59 residues per interface. Most of the individual interface parameters are clustered at the middle of the range which we call “standard-size” interfaces. Our observations indicate that there is relatively high composition (51%) of hydrophobic residues at the phycocyanin interfaces; most frequent amino acids in interfaces are Ala (11.4%), Leu (10.0%), Arg (9.5%) and Thr (8.3%). The analysis shows that about 42% of the total hydrogen bonds in the interfaces under consideration are involved in the formation of multiple hydrogen bonds; 52.8% of total number of hydrogen bonds is formed by water (as donor or acceptor; Figure 1); the hydrogen bonds across the interfaces are predominantly the O–N type; the largest numbers are side chain–side chain hydrogen bonds (55.9%) between the phycocyanin interfaces; most of hydrogen bonds possess distances in the region 2.8–4.2 Å, indicating their moderate and weak strength. The mean number of hydrophobic interactions per interface is 13.6 (max 30); the hydrophobic side chains make larger number of these interactions than side chains of charged and the hydrophilic amino acid. On average, there are about 3 salt bridges per interface in phycocyanin interfaces (max 7); less than one-tenth of the salt bridges in our database are networked, to form several triads, and the remaining are isolated ones. Most salt bridges (~80%) contain at least one hydrogen bond between the atoms in their side-chain charged groups; there is no preferred combination of donors and acceptors. The stability of a non-covalent complex is usually related to the complexation energy, which is proportional to the strength of the interactions involved. Analysis shows that hydrogen bond energies contribute to about 88% to the total energy. Van der Waals and electrostatic energy contributes to 9.3% and 1.9% on average in these complexes, respectively. Thus, hydrogen bonds contribute maximally towards the stability of protein–protein complexes. Results show the total binding energy is more for large phycocyanin interfaces. The normalized energy per residue was less than -16 kJ/mol, while most of them have energy in the range from 6 to 14 kJ/mol. The non-covalent interacting residues in phycocyanin protein interfaces were found to be highly conserved (ConSurfserver: http://consurf.tau.ac.il/2016/); salt bridge forming residues have average conservation scores 7.3; for those involved in hydrogen bonds is 7.0; the amino acid residues forming hydrophobic interactions and water-bridged hydrogen bonds both have average conservation scores of 5.9 (on scale 1–9). Obtained results might contribute to the understanding of structural stability of this class of evolutionary essential proteins with increased practical application and future designs of novel protein–bioactive compound interactions

Development of an Educational Game : Augmented Reality Approach to Edutainment

In this paper, the authors examine the problems, capabilities, and benefits of implementing augmented reality technologies in higher education and integrating them into formal e-learning in the form of edutainment. The main goal is to design and develop an educational interactive game that features augmented reality and would enrich the teaching process with interesting content as well as motivate students and stimulate their acquisition of knowledge. The developed game is based on current internet mobile technologies, with AR aspects realized through the use of the Vuforia platform, and is implemented as a part of a smart classroom. It includes a web application for teachers to create tasks, small parts of the curriculum that are being tested, a mobile application that students use to interact with the game and solve tasks, an augmented reality module that supports distance learning and a component for integration with Moodle LMS. This paper will focus on the AR aspects of the game and the benefits that can be gained with its use in education. The game has been implemented within the educational process at Faculty of Organizational Sciences, University of Belgrade

Computational analysis of non-covalent interactions in phycocyanin subunit interfaces

Phycocyanins (C-phycocyanin and allophycocyanin) are stable water-soluble trimers (αβ)3 or hexamers (αβ)6, containing dark-blue covalently attached phycocyanobilin chromophore with variety of pharmacological properties. Molecular forces (non-covalent interactions) responsible for the observed differences in thermal and chemical stability of different phycocyanin complexes are not completely understood 1. In this study, we used the manually curated non-redundant dataset of 118 interfaces from 20 X-ray phycocyanin structures (PDB ID codes: 1all, 1b33, 1kn1, 2vjt, 3dbj, 4f0u, 4po5,4rmp, 1cpc, 1gh0, 1f99, 1jbo, 1phn, 2bv8, 2vml, 3o18, 4l1e, 4lm6, 4lms, 4yjj) to gain additional insight to this phenomenon using a robust inter-atomic non-covalent interaction analyzing tool PPCheck (http://caps.ncbs.res.in/ppcheck). For our dataset, the mean interface area was 1088 Å2 and there were on average 59 residues per interface. Most of the individual interface parameters are clustered at the middle of the range which we call “standard-size” interfaces. Our observations indicate that there is relatively high composition (51%) of hydrophobic residues at the phycocyanin interfaces; most frequent amino acids in interfaces are Ala (11.4%), Leu (10.0%), Arg (9.5%) and Thr (8.3%). The analysis shows that about 42% of the total hydrogen bonds in the interfaces under consideration are involved in the formation of multiple hydrogen bonds; 52.8% of total number of hydrogen bonds is formed by water (as donor or acceptor; Figure 1); the hydrogen bonds across the interfaces are predominantly the O–N type; the largest numbers are side chain–side chain hydrogen bonds (55.9%) between the phycocyanin interfaces; most of hydrogen bonds possess distances in the region 2.8–4.2 Å, indicating their moderate and weak strength. The mean number of hydrophobic interactions per interface is 13.6 (max 30); the hydrophobic side chains make larger number of these interactions than side chains of charged and the hydrophilic amino acid. On average, there are about 3 salt bridges per interface in phycocyanin interfaces (max 7); less than one-tenth of the salt bridges in our database are networked, to form several triads, and the remaining are isolated ones. Most salt bridges (~80%) contain at least one hydrogen bond between the atoms in their side-chain charged groups; there is no preferred combination of donors and acceptors. The stability of a non-covalent complex is usually related to the complexation energy, which is proportional to the strength of the interactions involved. Analysis shows that hydrogen bond energies contribute to about 88% to the total energy. Van der Waals and electrostatic energy contributes to 9.3% and 1.9% on average in these complexes, respectively. Thus, hydrogen bonds contribute maximally towards the stability of protein–protein complexes. Results show the total binding energy is more for large phycocyanin interfaces. The normalized energy per residue was less than -16 kJ/mol, while most of them have energy in the range from 6 to 14 kJ/mol. The non-covalent interacting residues in phycocyanin protein interfaces were found to be highly conserved (ConSurfserver: http://consurf.tau.ac.il/2016/); salt bridge forming residues have average conservation scores 7.3; for those involved in hydrogen bonds is 7.0; the amino acid residues forming hydrophobic interactions and water-bridged hydrogen bonds both have average conservation scores of 5.9 (on scale 1–9). Obtained results might contribute to the understanding of structural stability of this class of evolutionary essential proteins with increased practical application and future designs of novel protein–bioactive compound interactions

Anion-π interactions in phycocyanin interfaces: a computational analysis

We investigated 321 possible anion-π interactions in a data set consisting of different subunit interfaces in 20 phycocyanins PDB structures. We observed that phycocyanobilin tetrapyrrole chromophore is capable of forming anion-π interactions only as an anion. It was found that Tyr is the most common aromatic donor. Although presented in the examined set of interfaces, Trp does not take part in anion-π interactions. Asp-Tyr is the most common anion-π pair, while Glu-His pair does not exist in our data set. Distance examination revealed that anion-π interactions between amino acid residues appear in the range of 3-7 Å, with the average value around 5 Å. The angle between carboxylate and aromatic ring points preference toward higher values, with a peak at 90° and average value around 66°. Interestingly, much less represented anion-π contacts including chromophore show higher values of distance and lower values of this angle. Ab initio calculations revealed that interaction energies lay in the range from +0.3 to −14 kcal mol−1, with generally much higher values for anion-π interaction pairs between amino acid residues compared to the chromophore including interactions. The most common (>50%) anion-π residue in the stabilization protein centers is Phe, while Glu and His are not presented at all. Anion-π interacting residues have high average conservation score of 7.7, which is especially pronounced for anion residues. The highest conservation score is observed for Asp and the lowest for Phe. Anion-π interacting residues show a preference for buried regions. Almost half of the residues involved in anion-π interactions are also part of hotspot regions, but only Asp, Phe, and Tyr. Further, in approximately one-fifth of anion-π interaction pairs, both of the residues come from the same hot-spot region and these are exclusively Asp-Tyr contacts. To conclude, a high percentage of anion-π interacting pairs in stabilization centers, their high presence in hot-spot regions and high conservation score, together with the favorable energy profile, imply that these interactions might have a significant role in the stability of phycocyanin oligomers

Open Innovation and Crowdsourcing: Challenges and Opportunities for Serbian Railways

The paper presents research that proposes prototype solutions based on open innovations, the Internet of Things, and crowdsourcing, which can increase traffic safety and reduce human casualties and material damage. The paper's authors conducted the research in cooperation with the Faculty of Organizational Sciences (FON) students in Belgrade and railway experts. FON students were presented with seven typical situations on the railway in Serbia. Traffic safety is often endangered, with human casualties and significant material damage, and the cause of these negative phenomena and accidents is not the railway. Traditional technical-technological solutions to these traffic problems to increase safety are extremely expensive and functionally complex, so they cannot be comprehensive, universal, and global. After the research, prototype solutions based on crowdsourcing principles were proposed, based on open innovations and the Internet of Things, to reduce the number and consequences of such characteristic situations on the railway. The research results confirm that open innovations based on crowdsourcing and the Internet of Things can increase safety in specific segments of railway traffic

ANALIZA PRIMENE I IZGRADNJE BRENDA KAO INSTRUMENTA ZA STICANJE KONKURENTSKE PREDNOSTI - PRIMER TRŽIŠTA RESTORANA U NOVOM SADU

Usluge su postale važan sastavni deo nacionalnih ekonomija, naročito u visoko razvijenim zemljama. Stoga je neophodnost istraživanja poslovanja i marketinga u uslužnim delatnostima veoma izražena. Prepoznatljiv, snažan brend sastoji se od pozitivnih, konzistentnih percepcija potrošača o ponudi koje je diferenciraju od konkurenata. Istovremeno, prepoznatljiv brend u svesti potrošača smanjuje rizik donošenja pogrešne odluke pri kupovini. Usled brojne direktne i indirektne konkurencije, u restoraterskim uslugama, izgradnja snažnog brenda je važna za postizanje zadovoljstva potrošača, njihovo prevođenje u lojalne potrošače i ostvarenje prednosti nad konkurentima. Ovaj rad ima za cilj da predstavi stavove menadžera restorana po pitanju kreiranja brenda u svrhu unapređenja poslovanja restoraterskih uslužnih preduzeća, kao i da istraži koliki je stepen razumevanja i primene, u literaturi poznatih, principa izgradnje brenda u restoranima, na tržištu Novog Sada. Istraživanje je sprovedeno na uzorku od 17 restorana u Novom Sadu, izabranih metodom „prigodnog“ uzorkovanja. Istraživanje je sprovedeno metodom anketiranja i intervjuisanja menadžera restorana, zaduženih za nastup restorana na tržištu i odnose sa potrošačima

Aromatična π-mreža u interfejsima Sm/LSm proteina

In this work, we have analyzed the influence of π-π interactions on stability and properties of Sm/LSm assemblies. The residues were found to be involved in π-π interactions much more frequently than Tyr or His. Similarly, the Phe-Phe π-π interacting pair had the highest frequency of occurrence. Furthermore, a significant number of π-networks were observed at the interface of Sm/LSm proteins. Generally speaking, the distance between the interacting pairs was in the range of 5-6 Å. 3π and 7π-networks were found to frequently have plane-plane angles less than 60º. Solvent accessibility pattern of Sm/LSm proteins revealed that all of the interacting residues were from buried areas. Moreover, most of the π-π interacting residues of Sm/LSm proteins were evolutionary conserved and were in the strand regions. A high percentage of these residues could be considered as stabilization centers that (significantly) contribute to the net stability of Sm/LSm proteins.U ovom radu smo analizirali uticaj π-π interakcija na stabilnost i osobine Sm/LSm proteinskih agregata. Ostatak fenilalanina znatno češće uzima učešće u π-π interakcijama u odnosu na His i Tyr. Slično, Phe-Phe π-π interagujući parovi su najučestaliji. Prepoznat je značajan broj π-mreža u interfejsima Sm/LSm proteinima. U većini slučajeva, rastojanje između interagujućih parova aminokiselina bilo je u opsegu 5-6 Å. Za 3π i 7π-mreže, prsten-prsten uglovi manji od 60º su bili učestaliji. Razmatrajući delove Sm/LSm proteina dostupne rastvaraču, može se zaključiti da se svi interagujući parovi nalaze u unutrašnjim regionima. Pored toga, većina π-π interagujućih aminokiselinskih ostataka je evoluciono konzervativan i nalazi se u regionima sa nabranom strukturom. Veliki broj ovih ostataka se može smatrati stabilizacionim centrima, koji (značajno) doprinose ukupnoj stabilnost Sm/LSm proteina

IoT Game-based Learning Model in Education

The subject of this paper is the development of a game-based learning model based on the Internet of Things (IoT). The main problem discussed in the paper is to investigate the possibility of implementing a game-based learning model in an interactive educational environment that will increase student interest and enhance learning outcomes. The developed model will be based on ubiquitous computing technologies and integrate IoT, mobile, and augmented reality technologies. The proposed model integrates with existing components of the educational infrastructure. As part of the model evaluation, testing and measurement of relevant parameters that affect the effectiveness of the proposed model was carried out

О значају π−π интеракција у структурној стабилности фикоцијанина

The influences of π−π interactions in phycocyanin proteins and their environmental preferences were analyzed. The observations indicate that the majority of the aromatic residues in phycocyanin proteins are involved in π−π interactions. Phenylalanine (Phe) and tyrosine (Tyr) residues were found to be involved in π–π interactions much more frequently than tryptophan (Trp) or histidine (His). Similarly, the Phe−Phe and Tyr−Tyr π–π interacting pair had the highest frequency of occurrence. In addition to π-π interactions, the aromatic residues also form π-networks in phycocyanins. The π–π interactions are most favourable at the pair distance range of 5.5–7 Å, with a clear preference for T-shaped ring arrangements. Using ab initio calculations, we observed that most of the π−π interactions possess energy from 0 to −10 kJ mol-1. Stabilization centres for these proteins showed that all residues found in π−π interactions are important in locating one or more such centres. π−π interacting residues are evolutionary conserved. The results obtained from this study will be beneficial in further understanding the structural stability and eventual development of protein engineering of phycocyanins.Анализирани су утицаји π−π интеракција у протеинима фикоцијанинима и њихове преференције ка окружењу. Запажања показују да је већина ароматичних остатака у протеинима фикоцијанинима укључена у π−π интеракције. Утврђено је да су остаци фенилаланина (Phe) и тирозина (Tyr) много чешће укључени у π–π интеракције него триптофана (Trp) или хистидина (His). Слично томе, интерагујући π–π парови Phe−Phe и Tyr−Tyr имали су највећу учесталост појављивања. Додатно, ароматични остаци такође стварају π-мреже у фикоцијанинима. π–π интеракције су најповољније у распону дистанци парова од 5,5–7 Å, с јасном склоношћу за распоред прстенова у облику слова Т. Користећи ab initio прорачуне, приметили смо да већина π−π интеракција има енергију у распону од 0 до −10 kJ mol-1. Стабилизациони центри ових протеина показали су да су сви остаци пронађени у π−π интеракцијама важни у лоцирању једног или више таквих центара. π−π интеракциони остаци су еволутивно конзервирани. Резултати добивени овом студијом биће од користи у даљем разумевању структурне стабилности и евентуалном развоју протеинског инжењеринга фикоцијанина

AROMATIC Π-NETWORKS IN SM/LSM PROTEIN INTERFACES

In this work, we have analyzed the influence of π–π interactions on stability and properties of Sm/LSm assemblies. Phe residues were found to be involved in π–π interactions much more frequently than Tyr or His. Similarly, the Phe–Phe π–π interacting pair had the highest frequency of occurrence. Furthermore, a significant number of π-networks were observed at the interface of Sm/LSm proteins. Generally speaking, the distance between the interacting pairs was in the range of 5–6 Å. 3π and 7π-networks were found to frequently have plane-plane angles less than 60º. Solvent accessibility pattern of Sm/LSm proteins revealed that all of the interacting residues were from buried areas. Moreover, most of the π–π interacting residues of Sm/LSm proteins were evolutionary conserved and were in the strand regions. A high percentage of these residues could be considered as stabilization centers that (significantly) contribute to the net stability of Sm/LSm proteins. AROMATIČNA Π-MREŽA U INTERFEJSIMA SM/LSM PROTEINA U ovom radu smo analizirali uticaj π–π interakcija na stabilnost i osobine Sm/LSm proteinskih agregata. Ostatak fenilalanina znatno češće uzima učešće u π–π interakcijama u odnosu na His i Tyr. Slično, Phe–Phe π–π interagujući parovi su najučestaliji. Prepoznat je značajan broj π-mreža u interfejsima Sm/LSm proteinima. U većini slučajeva, rastojanje između interagujućih parova aminokiselina bilo je u opsegu 5–6 Å. Za 3π i 7π-mreže, prsten-prsten uglovi manji od 60º su bili učestaliji. Razmatrajući delove Sm/LSm proteina dostupne rastvaraču, može se zaključiti da se svi interagujući parovi nalaze u unutrašnjim regionima. Pored toga, većina π–π interagujućih aminokiselinskih ostataka je evoluciono konzervativan i nalazi se u regionima sa nabranom strukturom. Veliki broj ovih ostataka se može smatrati stabilizacionim centrima, koji (značajno) doprinose ukupnoj stabilnost Sm/LSm proteina