TY  - JOUR
AU  - Breberina, Luka
AU  - Nikolić, Milan
AU  - Stojanović, Srđan
AU  - Zlatović, Mario
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6502
AB  - 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.
AB  - 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.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - On the importance of π–π interactions in structural stability of phycocyanins
T1  - О значају π−π интеракција у структурној стабилности фикоцијанина
VL  - 88
IS  - 5
SP  - 481
EP  - 494
DO  - 10.2298/JSC221201008B
ER  - 

@article{
author = "Breberina, Luka and Nikolić, Milan and Stojanović, Srđan and Zlatović, Mario",
year = "2023",
abstract = "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.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "On the importance of π–π interactions in structural stability of phycocyanins, О значају π−π интеракција у структурној стабилности фикоцијанина",
volume = "88",
number = "5",
pages = "481-494",
doi = "10.2298/JSC221201008B"
}

Breberina, L., Nikolić, M., Stojanović, S.,& Zlatović, M.. (2023). On the importance of π–π interactions in structural stability of phycocyanins. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 88(5), 481-494.
https://doi.org/10.2298/JSC221201008B

Breberina L, Nikolić M, Stojanović S, Zlatović M. On the importance of π–π interactions in structural stability of phycocyanins. in Journal of the Serbian Chemical Society. 2023;88(5):481-494.
doi:10.2298/JSC221201008B .

Breberina, Luka, Nikolić, Milan, Stojanović, Srđan, Zlatović, Mario, "On the importance of π–π interactions in structural stability of phycocyanins" in Journal of the Serbian Chemical Society, 88, no. 5 (2023):481-494,
https://doi.org/10.2298/JSC221201008B . .

TY  - JOUR
AU  - Breberina, Luka M.
AU  - Nikolić, Milan R.
AU  - Stojanović, Srđan
AU  - Zlatović, Mario
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5330
AB  - The influences of cation−π interactions in phycocyanin proteins and their environmental preferences were analyzed. The number of interactions formed by arginine showed to be higher than those formed by the lysine in the cationic group, while histidine is comparatively higher than phenylalanine and N-terminal residue in the π group. Arg−Tyr and Arg−Phe interacting pairs are predominant among the various pairs analyzed. Cation−π interactions are distance-dependent and can be realized above a wider area above the π ring. We analyzed the energy contribution resulting from cation−π interactions using ab initio calculations. The energy contribution resulting from the most frequent cation−π interactions was in the lower range of strong hydrogen bonds. The results showed that, while most of their interaction energies lay ranged from − 2 to − 8 kcal/mol, those energies could be up to −12− 12 kcal/mol. Stabilization centers for these proteins showed that all residues found in cation−π interactions are important in locating one or more of such centers. In the cation–π interacting residues, 54% of the amino acid residues involved in these interactions might be conserved in phycocyanins. From this study, we infer that cation−π forming residues play an important role in the stability of the multiply commercially used phycocyanin proteins and could help structural biologists and medicinal chemists to design better and safer drugs.
PB  - Elsevier
T2  - Computational Biology and Chemistry
T1  - Influence of cation−π interactions to the structural stability of phycocyanin proteins: A computational study
VL  - 100
IS  - 107752
DO  - 10.1016/j.compbiolchem.2022.107752
ER  - 

@article{
author = "Breberina, Luka M. and Nikolić, Milan R. and Stojanović, Srđan and Zlatović, Mario",
year = "2022",
abstract = "The influences of cation−π interactions in phycocyanin proteins and their environmental preferences were analyzed. The number of interactions formed by arginine showed to be higher than those formed by the lysine in the cationic group, while histidine is comparatively higher than phenylalanine and N-terminal residue in the π group. Arg−Tyr and Arg−Phe interacting pairs are predominant among the various pairs analyzed. Cation−π interactions are distance-dependent and can be realized above a wider area above the π ring. We analyzed the energy contribution resulting from cation−π interactions using ab initio calculations. The energy contribution resulting from the most frequent cation−π interactions was in the lower range of strong hydrogen bonds. The results showed that, while most of their interaction energies lay ranged from − 2 to − 8 kcal/mol, those energies could be up to −12− 12 kcal/mol. Stabilization centers for these proteins showed that all residues found in cation−π interactions are important in locating one or more of such centers. In the cation–π interacting residues, 54% of the amino acid residues involved in these interactions might be conserved in phycocyanins. From this study, we infer that cation−π forming residues play an important role in the stability of the multiply commercially used phycocyanin proteins and could help structural biologists and medicinal chemists to design better and safer drugs.",
publisher = "Elsevier",
journal = "Computational Biology and Chemistry",
title = "Influence of cation−π interactions to the structural stability of phycocyanin proteins: A computational study",
volume = "100",
number = "107752",
doi = "10.1016/j.compbiolchem.2022.107752"
}

Breberina, L. M., Nikolić, M. R., Stojanović, S.,& Zlatović, M.. (2022). Influence of cation−π interactions to the structural stability of phycocyanin proteins: A computational study. in Computational Biology and Chemistry
Elsevier., 100(107752).
https://doi.org/10.1016/j.compbiolchem.2022.107752

Breberina LM, Nikolić MR, Stojanović S, Zlatović M. Influence of cation−π interactions to the structural stability of phycocyanin proteins: A computational study. in Computational Biology and Chemistry. 2022;100(107752).
doi:10.1016/j.compbiolchem.2022.107752 .

Breberina, Luka M., Nikolić, Milan R., Stojanović, Srđan, Zlatović, Mario, "Influence of cation−π interactions to the structural stability of phycocyanin proteins: A computational study" in Computational Biology and Chemistry, 100, no. 107752 (2022),
https://doi.org/10.1016/j.compbiolchem.2022.107752 . .

TY  - CONF
AU  - Breberina, Luka
AU  - Stojanović, Srđan
AU  - Nikolić, Milan
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6504
AB  - 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.
PB  - Belgrade : Serbian Biochemical Society
C3  - Proceedings - Serbian Biochemical Society Ninth Conference with international participation, “Diversity in Biochemistry”, 14-16.11.2019. Belgrade, Serbia
T1  - Anion-π interactions in phycocyanin interfaces: a computational analysis
SP  - 80
EP  - 81
UR  - https://hdl.handle.net/21.15107/rcub_cer_6504
ER  - 

@conference{
author = "Breberina, Luka and Stojanović, Srđan and Nikolić, Milan",
year = "2019",
abstract = "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.",
publisher = "Belgrade : Serbian Biochemical Society",
journal = "Proceedings - Serbian Biochemical Society Ninth Conference with international participation, “Diversity in Biochemistry”, 14-16.11.2019. Belgrade, Serbia",
title = "Anion-π interactions in phycocyanin interfaces: a computational analysis",
pages = "80-81",
url = "https://hdl.handle.net/21.15107/rcub_cer_6504"
}

Breberina, L., Stojanović, S.,& Nikolić, M.. (2019). Anion-π interactions in phycocyanin interfaces: a computational analysis. in Proceedings - Serbian Biochemical Society Ninth Conference with international participation, “Diversity in Biochemistry”, 14-16.11.2019. Belgrade, Serbia
Belgrade : Serbian Biochemical Society., 80-81.
https://hdl.handle.net/21.15107/rcub_cer_6504

Breberina L, Stojanović S, Nikolić M. Anion-π interactions in phycocyanin interfaces: a computational analysis. in Proceedings - Serbian Biochemical Society Ninth Conference with international participation, “Diversity in Biochemistry”, 14-16.11.2019. Belgrade, Serbia. 2019;:80-81.
https://hdl.handle.net/21.15107/rcub_cer_6504 .

Breberina, Luka, Stojanović, Srđan, Nikolić, Milan, "Anion-π interactions in phycocyanin interfaces: a computational analysis" in Proceedings - Serbian Biochemical Society Ninth Conference with international participation, “Diversity in Biochemistry”, 14-16.11.2019. Belgrade, Serbia (2019):80-81,
https://hdl.handle.net/21.15107/rcub_cer_6504 .

TY  - JOUR
AU  - Breberina, Luka
AU  - Zlatović, Mario
AU  - Nikolić, Milan
AU  - Stojanović, Srđan
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3233
AB  - Protein‐protein interactions are an important phenomenon in biological processes and functions. We used the manually curated non‐redundant dataset of 118 phycocyanin interfaces to gain additional insight into this phenomenon using a robust inter‐atomic non‐covalent interaction analyzing tool PPCheck. Our observations indicate that there is a relatively high composition of hydrophobic residues at the interfaces. Most of the interface residues are clustered at the middle of the range which we call “standard‐size” interfaces. Furthermore, the multiple interaction patterns founded in the present study indicate that more than half of the residues involved in these interactions participate in multiple and water‐bridged hydrogen bonds. Thus, hydrogen bonds contribute maximally towards the stability of protein‐protein complexes. The analysis shows that hydrogen bond energies contribute to about 88 % to the total energy and it also increases with interface size. Van der Waals (vdW) energy contributes to 9.3 %±1.7 % on average in these complexes. Moreover, there is about 1.9 %±1.5 % contribution by electrostatic energy. Nevertheless, the role by vdW and electrostatic energy could not be ignored in interface binding. Results show that the total binding energy is more for large phycocyanin interfaces. The normalized energy per residue was less than −16 kJ mol−1, while most of them have energy in the range from −6 to −14 kJ mol−1. The non‐covalent interacting residues in these proteins were found to be highly conserved. 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.
PB  - Wiley
T2  - Molecular Informatics
T1  - Computational Analysis of Non‐covalent Interactions in Phycocyanin Subunit Interfaces
VL  - 38
IS  - 11-12
SP  - 1800145
DO  - 10.1002/minf.201800145
ER  - 

@article{
author = "Breberina, Luka and Zlatović, Mario and Nikolić, Milan and Stojanović, Srđan",
year = "2019",
abstract = "Protein‐protein interactions are an important phenomenon in biological processes and functions. We used the manually curated non‐redundant dataset of 118 phycocyanin interfaces to gain additional insight into this phenomenon using a robust inter‐atomic non‐covalent interaction analyzing tool PPCheck. Our observations indicate that there is a relatively high composition of hydrophobic residues at the interfaces. Most of the interface residues are clustered at the middle of the range which we call “standard‐size” interfaces. Furthermore, the multiple interaction patterns founded in the present study indicate that more than half of the residues involved in these interactions participate in multiple and water‐bridged hydrogen bonds. Thus, hydrogen bonds contribute maximally towards the stability of protein‐protein complexes. The analysis shows that hydrogen bond energies contribute to about 88 % to the total energy and it also increases with interface size. Van der Waals (vdW) energy contributes to 9.3 %±1.7 % on average in these complexes. Moreover, there is about 1.9 %±1.5 % contribution by electrostatic energy. Nevertheless, the role by vdW and electrostatic energy could not be ignored in interface binding. Results show that the total binding energy is more for large phycocyanin interfaces. The normalized energy per residue was less than −16 kJ mol−1, while most of them have energy in the range from −6 to −14 kJ mol−1. The non‐covalent interacting residues in these proteins were found to be highly conserved. 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.",
publisher = "Wiley",
journal = "Molecular Informatics",
title = "Computational Analysis of Non‐covalent Interactions in Phycocyanin Subunit Interfaces",
volume = "38",
number = "11-12",
pages = "1800145",
doi = "10.1002/minf.201800145"
}

Breberina, L., Zlatović, M., Nikolić, M.,& Stojanović, S.. (2019). Computational Analysis of Non‐covalent Interactions in Phycocyanin Subunit Interfaces. in Molecular Informatics
Wiley., 38(11-12), 1800145.
https://doi.org/10.1002/minf.201800145

Breberina L, Zlatović M, Nikolić M, Stojanović S. Computational Analysis of Non‐covalent Interactions in Phycocyanin Subunit Interfaces. in Molecular Informatics. 2019;38(11-12):1800145.
doi:10.1002/minf.201800145 .

Breberina, Luka, Zlatović, Mario, Nikolić, Milan, Stojanović, Srđan, "Computational Analysis of Non‐covalent Interactions in Phycocyanin Subunit Interfaces" in Molecular Informatics, 38, no. 11-12 (2019):1800145,
https://doi.org/10.1002/minf.201800145 . .

TY  - CONF
AU  - Breberina, Luka
AU  - Nikolić, Milan
AU  - Stojanović, Srđan
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3544
AB  - 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.
PB  - Serbian Biochemical Society
C3  - Serbian Biochemical Society Eighth Conference with international participation, “Coordination in Biochemistry and Life”, University of Novi Sad – Rectorate Hall, 16.11.2018. Novi Sad, Serbia
T1  - Computational analysis of non-covalent interactions in phycocyanin subunit interfaces
SP  - 119
EP  - 120
UR  - https://hdl.handle.net/21.15107/rcub_cer_3544
ER  - 

@conference{
author = "Breberina, Luka and Nikolić, Milan and Stojanović, Srđan",
year = "2018",
abstract = "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.",
publisher = "Serbian Biochemical Society",
journal = "Serbian Biochemical Society Eighth Conference with international participation, “Coordination in Biochemistry and Life”, University of Novi Sad – Rectorate Hall, 16.11.2018. Novi Sad, Serbia",
title = "Computational analysis of non-covalent interactions in phycocyanin subunit interfaces",
pages = "119-120",
url = "https://hdl.handle.net/21.15107/rcub_cer_3544"
}

Breberina, L., Nikolić, M.,& Stojanović, S.. (2018). Computational analysis of non-covalent interactions in phycocyanin subunit interfaces. in Serbian Biochemical Society Eighth Conference with international participation, “Coordination in Biochemistry and Life”, University of Novi Sad – Rectorate Hall, 16.11.2018. Novi Sad, Serbia
Serbian Biochemical Society., 119-120.
https://hdl.handle.net/21.15107/rcub_cer_3544

Breberina L, Nikolić M, Stojanović S. Computational analysis of non-covalent interactions in phycocyanin subunit interfaces. in Serbian Biochemical Society Eighth Conference with international participation, “Coordination in Biochemistry and Life”, University of Novi Sad – Rectorate Hall, 16.11.2018. Novi Sad, Serbia. 2018;:119-120.
https://hdl.handle.net/21.15107/rcub_cer_3544 .

Breberina, Luka, Nikolić, Milan, Stojanović, Srđan, "Computational analysis of non-covalent interactions in phycocyanin subunit interfaces" in Serbian Biochemical Society Eighth Conference with international participation, “Coordination in Biochemistry and Life”, University of Novi Sad – Rectorate Hall, 16.11.2018. Novi Sad, Serbia (2018):119-120,
https://hdl.handle.net/21.15107/rcub_cer_3544 .

TY  - JOUR
AU  - Breberina, Luka M.
AU  - Milčić, Miloš
AU  - Nikolić, Milan
AU  - Stojanović, Srđan
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1693
AB  - We have analyzed the influence of anion-pi interactions to the stability of Sm/LSm assemblies. The side chain of Glu is more likely to be in anion-pi interactions than Asp. Phe has the highest occurrence in these interactions than the other two pi residues. Among the anion-pi residue pairs, Glu-Phe residue pair showed the maximum number of anion-pi. We have found hot-spot residues forming anion-pi interactions, and Glu-Phe is the most common hot-spot interacting pair. The significant numbers of anion-pi interacting residues identified in the dataset were involved in the formation of multiple anion-pi interactions. More than half of the residues involved in these interactions are evolutionarily conserved. The anion-pi interaction energies are distance and orientation dependent. It was found that anion-pi interactions showed energy less than -15 kcal mol(-1), and most of them have energy in the range -2 to -9 kcal mol(-1). Solvent accessibility pattern of Sm/LSm proteins reveals that all of the interacting residues are preferred to be in buried regions. Most of the interacting residues preferred to be in strand. A significant percentage of anion-pi interacting residues are located as stabilization centers and thus might provide additional stability to these proteins. The simultaneous interaction of anions and cations on different faces of the same pi-system has been observed. On the whole, the results presented in this work will be very useful for understanding the contribution of anion-pi interaction to the stability of Sm/LSm proteins.
PB  - Springer, New York
T2  - Journal of Biological Inorganic Chemistry
T1  - Contribution of anion-pi interactions to the stability of Sm/LSm proteins
VL  - 20
IS  - 3
SP  - 475
EP  - 485
DO  - 10.1007/s00775-014-1227-1
ER  - 

@article{
author = "Breberina, Luka M. and Milčić, Miloš and Nikolić, Milan and Stojanović, Srđan",
year = "2015",
abstract = "We have analyzed the influence of anion-pi interactions to the stability of Sm/LSm assemblies. The side chain of Glu is more likely to be in anion-pi interactions than Asp. Phe has the highest occurrence in these interactions than the other two pi residues. Among the anion-pi residue pairs, Glu-Phe residue pair showed the maximum number of anion-pi. We have found hot-spot residues forming anion-pi interactions, and Glu-Phe is the most common hot-spot interacting pair. The significant numbers of anion-pi interacting residues identified in the dataset were involved in the formation of multiple anion-pi interactions. More than half of the residues involved in these interactions are evolutionarily conserved. The anion-pi interaction energies are distance and orientation dependent. It was found that anion-pi interactions showed energy less than -15 kcal mol(-1), and most of them have energy in the range -2 to -9 kcal mol(-1). Solvent accessibility pattern of Sm/LSm proteins reveals that all of the interacting residues are preferred to be in buried regions. Most of the interacting residues preferred to be in strand. A significant percentage of anion-pi interacting residues are located as stabilization centers and thus might provide additional stability to these proteins. The simultaneous interaction of anions and cations on different faces of the same pi-system has been observed. On the whole, the results presented in this work will be very useful for understanding the contribution of anion-pi interaction to the stability of Sm/LSm proteins.",
publisher = "Springer, New York",
journal = "Journal of Biological Inorganic Chemistry",
title = "Contribution of anion-pi interactions to the stability of Sm/LSm proteins",
volume = "20",
number = "3",
pages = "475-485",
doi = "10.1007/s00775-014-1227-1"
}

Breberina, L. M., Milčić, M., Nikolić, M.,& Stojanović, S.. (2015). Contribution of anion-pi interactions to the stability of Sm/LSm proteins. in Journal of Biological Inorganic Chemistry
Springer, New York., 20(3), 475-485.
https://doi.org/10.1007/s00775-014-1227-1

Breberina LM, Milčić M, Nikolić M, Stojanović S. Contribution of anion-pi interactions to the stability of Sm/LSm proteins. in Journal of Biological Inorganic Chemistry. 2015;20(3):475-485.
doi:10.1007/s00775-014-1227-1 .

Breberina, Luka M., Milčić, Miloš, Nikolić, Milan, Stojanović, Srđan, "Contribution of anion-pi interactions to the stability of Sm/LSm proteins" in Journal of Biological Inorganic Chemistry, 20, no. 3 (2015):475-485,
https://doi.org/10.1007/s00775-014-1227-1 . .

TY  - JOUR
AU  - Breberina, Luka M.
AU  - Nikolić, Milan
AU  - Stojanović, Srđan
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1468
AB  - 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.
AB  - 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.
PB  - Univerzitet u Nišu
T2  - Facta universitatis - series: Physics, Chemistry and Technology
T1  - Aromatic π-networks in Sm/LSm protein interfaces
T1  - Aromatična π-mreža u interfejsima Sm/LSm proteina
VL  - 12
IS  - 1
SP  - 27
EP  - 39
DO  - 10.2298/FUPCT1401027B
ER  - 

@article{
author = "Breberina, Luka M. and Nikolić, Milan and Stojanović, Srđan",
year = "2014",
abstract = "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.",
publisher = "Univerzitet u Nišu",
journal = "Facta universitatis - series: Physics, Chemistry and Technology",
title = "Aromatic π-networks in Sm/LSm protein interfaces, Aromatična π-mreža u interfejsima Sm/LSm proteina",
volume = "12",
number = "1",
pages = "27-39",
doi = "10.2298/FUPCT1401027B"
}

Breberina, L. M., Nikolić, M.,& Stojanović, S.. (2014). Aromatic π-networks in Sm/LSm protein interfaces. in Facta universitatis - series: Physics, Chemistry and Technology
Univerzitet u Nišu., 12(1), 27-39.
https://doi.org/10.2298/FUPCT1401027B

Breberina LM, Nikolić M, Stojanović S. Aromatic π-networks in Sm/LSm protein interfaces. in Facta universitatis - series: Physics, Chemistry and Technology. 2014;12(1):27-39.
doi:10.2298/FUPCT1401027B .

Breberina, Luka M., Nikolić, Milan, Stojanović, Srđan, "Aromatic π-networks in Sm/LSm protein interfaces" in Facta universitatis - series: Physics, Chemistry and Technology, 12, no. 1 (2014):27-39,
https://doi.org/10.2298/FUPCT1401027B . .