Protein folding (Physics)

The initiation of reverse transcription of a retroviral RNA genome occurs by a tRNA primer bound near the 5' end of the genomic RNA at a position called the primer-binding site (PBS). To understand the molecular basis for this RNA-RNA interaction, the secondary structure of the leader RNA of the human immunodeficiency virus type 2 (HIV-2) RNA was analyzed. In vitro synthesized HIV-2 RNA was probed with various structure-specific enzymes and chemicals. A computer program was then used to predict the secondary structure consistent with these data. In addition, the nucleotide sequences of different HIV-2 isolates were used to screen for the occurrence of co- variation among putative base pairs. The primary sequences have diverged rapidly in some HIV-2 isolates, however, some strikingly conserved secondary structure elements were identified. Most nucleotides in the leader region are involved in base pairing. An exception is the PBS sequence, of which 15 out of 18 nucleotides are exposed in an internal loop. These findings suggest that the overall structure of the HIV-2 genome has evolved to facilitate an optimal interaction with its tRNA primer.

the number of disulfide bonds per residue are negatively correlated in proteins with short chains and uncorrelated in proteins with long chains. (4) The number of salt bridges per residue and per native contact increases with chain length. We interpret these observations as an indication that the constraints imposed by unfolding stability are less demanding in long proteins and they are further reduced by the competing requirement for stability against misfolding. In particular, disulfide bonds appear to be positively selected in short proteins, whereas they evolve in an effectively neutral way in long proteins.

the number of disulfide bonds per residue are negatively correlated in proteins with short chains and uncorrelated in proteins with long chains. (4) The number of salt bridges per residue and per native contact increases with chain length. We interpret these observations as an indication that the constraints imposed by unfolding stability are less demanding in long proteins and they are further reduced by the competing requirement for stability against misfolding. In particular, disulfide bonds appear to be positively selected in short proteins, whereas they evolve in an effectively neutral way in long proteins.

Inspired by protein folding, we explored the construction of three-dimensional structures and machines from onedimensional chains of simple building blocks. This approach not only allows us to recreate the self-replication mechanism introduced earlier, but also significantly simplifies the process. We introduced a new set of folding blocks that facilitate the formation of secondary structures such as α-helices and β-sheets, as well as more advanced tertiary and quaternary structures, including self-replicating machines. The introduction of rotational degrees of freedom leads to a reduced variety of blocks and, most importantly, reduces the overall size of the machines by a factor of five. In addition, we present a universal copier-constructor, a highly efficient selfreplicating mechanism composed of approximately 40 blocks, including the restictions posed on it. The paper also addresses evolutionary considerations, outlining several steps on the evolutionary ladder towards more sophisticated self-replicating systems. Finally, this study offers a clear rationale for nature's preference for onedimensional chains in constructing three-dimensional structures.

This study presents a theoretical model for a self-replicating mechanical system inspired by biological processes within living cells and supported by computer simulations. The model decomposes self-replication into core components, each of which is executed by a single machine constructed from a set of basic block types. Key functionalities such as sorting, copying, and building, are demonstrated. The model provides valuable insights into the constraints of selfreplicating systems. The discussion also addresses the spatial and timing behavior of the system, as well as its efficiency and complexity. This work provides a foundational framework for future studies on self-replicating mechanisms and their information-processing applications.

This article aims to assess the two competing models of features that have dominated the history of phonological theory for almost one century: the first, which originates from Trubetzkoy, allows both "privative" and "equipollent" contrasts; the second comes from Jakobson's strict binarism, and has been continued in generative phonology up to the present day. Firstly, it will be argued that the latter model suffers from at least three problems that follow from overgeneration, and make it impossible to provide a natural and unified account of systemic and processual markedness. Secondly, it will be shown how these problems can be given a straightforward solution through an approach based on privative elements, in which markedness becomes the result of operations acting on primary segments. Interestingly, such a view turns out to be remarkably compatible with recent findings in L1 acquisition, namely Kuhl's Native Language Magnet Theory. 1 I would like to thank Jean-Louis Aroui for his comments on the original draft of this article. I am also indebted to one anonymous reviewer and, especially, Yuni Kim, Edoardo Cavirani and Shanti Ulfsbjorninn for their input on two revised versions. I hope that their very useful remarks have been satisfactorily considered in this final version.

OBJECTIVES: To determine the frequency of death due to elevated serum alpha-fetoprotein (AFP ≥20 IU/ml) in HCV
patients suffering from HCC in Liaquat University Hospital, Hyderabad/Jamshoro
MATERIAL & METHODS: This case series study was conducted in the department of department of Medicine Liaquat
University Hospital, Hyderabad/Jamshoro, with six months from 4TH October 2014 to April 2014. All the patients with
hepatocellular carcinoma due to hepatitis C virus, raised alpha fetoprotein levels (20IU/ml), HCC newly or recent
diagnosed i.e. diagnosed within last 6m, tumour size more than or equal to 3cm, adult population (if they are having
underlying HCV related HCC) either gender were included in the study.
RESULTS: A total of 165 HCC patients were enrolled in this study with average age + SD 55.8+10.112 years.152(92.1%)
were male and 13(7.87%) were female. 92(55.7%) were middle class, 51(30.9%) patients were from rich families and
22(13.3%) consisted to poor class of socio-economic status. Mean duration + SD (range) of HCC was 12.53 + 7.23 (1 to 48
years). 29(17.5%) patients had tumor size < 3 cm, 66(40.0%) had tumor size 3 to 5 cm whereas 70(42.4%) patients had
tumor size > 5 cm. 32(19.3%) patients had normal serum alpha fetoprotein level (< 20 IU/ml), 38(23.0%) moderately
elevated alpha fetoprotein level (20 to 399 IU/ml) while 95(57.5%) patients had markedly elevated serum alpha fetoprotein
level(≥400 IU/ml). Overall mortality was seen in 68(41.1%). Tumor size > 5 cm and markedly elevated AFP (≥400 IU/ml),
duration of HCC were found to be significant causes and biomarkers of mortality in HCC patients respectively (p value 0.01,
< 0.0001).
CONCLUSION: HCC patients with elevated AFP levels determine a higher mortality rate, which appears to be attributable
to the growth promoting properties of AFP.
Key words: Hepatocellular carcinoma, Alpha feto-protein, HCV

α-Heliсes are the most frequently occurring elements of the secondary structure in water-soluble globular proteins. Their increased conformational stability is among the main reasons for the high thermal stability of proteins in thermophilic bacteria. In addition, α-helices are often involved in protein interactions with other proteins, nucleic acids, and the lipids of cell membranes. That is why the highly stable α-helical peptides used as highly active and specific inhibitors of protein–protein and other interactions have recently found more applications in medicine. Several different approaches have been developed in recent years to improve the conformational stability of α-helical peptides and thermostable proteins, which will be discussed in this review. We also discuss the methods for improving the permeability of peptides and proteins across cellular membranes and their resistance to intracellular protease activity. Special attention is given to the SEQOPT method ( http://nanobio.spbstu.ru/services/seqopt/ ), which is used to design conformationally stable short α-helices.

Recent studies have elucidated key principles governing folding and stability of α-helices in short peptides and globular proteins. In this chapter we review briefly those principles and describe a protocol for the de novo design of highly stable α-helixes using the SEQOPT algorithm. This algorithm is based on AGADIR, the statistical mechanical theory for helix-coil transitions in monomeric peptides, and the tunneling algorithm for global sequence optimization.

About fifty years ago, the Turing instability demonstrated that even simple reaction-diffusion systems might lead to spatial order and differentiation, while the Rayleigh-Benard instability showed that the maintenance of nonequilibrium might be the source of order in fluids subjected to a thermodynamic force above a critical value. Therefore, distance from global equilibrium in the form of magnitude of a thermodynamic force emerges as another constraint of stability; some systems may enhance perturbations, and evolve to highly organized states called the dissipative structures after a critical distance on the thermodynamic branch. Although the kinetics and transport coefficients represent short-range interactions, chemical instabilities may lead to long-range order and coherent time behavior, such as a chemical clock, known as Hopf bifurcation. Stability analyses of linear and nonlinear modes for stationary homogeneous systems are useful in understanding the formation of organized s...

Amyloidogenic diseases, such as, Alzheimer&#x27;s are caused by adsorption and aggregation of partially unfolded proteins. Adsorption of proteins is a concern in design of biomedical devices, such as dialysis membranes. Protein adsorption is often accompanied by ...

A theoretical study has shown that the occurrence of various structural elements in stable folds of random copolymers is exponentially dependent on the own energy of the element. A similar occurrence‐on‐energy dependence is observed in globular proteins1 from the level of amino acid conformations to the level of overall architectures. Thus, the structural features stabilized by many random sequences are typical of globular proteins while the features rarely observed in proteins are those which are stabilized by only a minor part of the random sequences. © 1995 Wiley‐Liss, Inc.

We propose a scenario for the prebiotic co-evolution of RNA and of fast folding proteins with large entropy gaps as observed today. We show from very general principles that the folding and unfolding of the proteins synthesized by RNA can function as a heat pump. Rock surfaces can facilitate the folding of amino acid chains having polar and hydrophobic residues, with an accompanying heat loss to the surrounding rock. These chains then absorb heat from the soup as they unfold. This opens the way to the enhancement of RNA replication rates, by the enzymatic action of folded proteins present in greater numbers at reduced temperatures. This gives an evolutionary advantage to those RNA coding amino acid sequences with non-degenerate folded states which would provide the most efficient refrigeration.

The aberrant formation of α-synuclein (Syn) aggregates, varying in size, structure and morphology, has been linked to the development of Parkinson’s disease. In the early stages of Syn aggregation, large protein amyloid aggregates with sizes &gt; 100 nm in hydrodynamic radius have been noticed. These low overall abundant large Syn aggregates are notoriously difficult to study by conventional biophysical methods. Due to the growing importance of studying the early stages of Syn aggregation, we developed a strategy to achieve this purpose, which is the study of the initial effect of the Syn protein aqueous solutions temperature rise. Therefore, the increase of the Syn aqueous solutions entropy by the initial effect of the temperature rise led to the exposure of the protein hydrophobic tyrosyl groups by not interfering with this amyloid protein aggregation. As an attempt to interpret the degree of the referred protein tyrosyl groups exposure, the classic rotameric conformations of the ...

We monitor early stages of beta-amyloid (A1-40) aggregation, one of key processes leading to Alzheimer's disease (AD), in the presence of high glucose concentrations by measuring A1-40 intrinsic fluorescence. The multiple peaks and their shifts observed in the time-resolved emission spectra (TRES) reveal the impact of glycation on Aβ1-40 oligomerisation. The results show that formation of the advanced glycation end products (AGEs) alters the aggregation pathway. These changes are highly relevant to our understanding of the pathophysiology of AD and the implication of AGE and diabetes in these pathways.

A stable conformer of Escherichia coli tRNA Glu , obtained in the absence of Mg 2+ , is inactive in the aminoacylation reaction. Probing it with diethylpyrocarbonate, dimethyl sulfate and ribonuclease V1 revealed that it has a hairpin structure with two internal loops; the helical segments at both extremities have the same structure as the acceptor stem and the anticodon arm of the native conformer of tRNA Glu and the middle helix is formed of nucleotides from the D-loop (G15-C20:2) and parts of the T-loop and stem (G51-C56), with G19 bulging out. This model is consistent with other known properties of this inactive conformer, including its capacity to dimerize. Therefore, this tRNA requires magnesium to acquire a conformation that can be aminoacylated, as others require a posttranscriptional modification to reach this active conformation.

Amyloidogenic diseases, such as, Alzheimer&#x27;s are caused by adsorption and aggregation of partially unfolded proteins. Adsorption of proteins is a concern in design of biomedical devices, such as dialysis membranes. Protein adsorption is often accompanied by ...

Experimental evidence suggests that protein molecules adsorbed to hydrophobic surfaces are thermally more stable than in the bulk. To understand this observation, adsorption of a model lattice protein on hydrophobic surfaces was studied using Monte Carlo simulations. It was ...

Structure of a protein relates to its function and it is well understood that during the folding process, the nonpolar side chains get buried due to hydrophobic effects and the main-chains form N-H•••O=C hydrogen bonds. Experimental and theoretical evidences [1] claim that the electrostatic energy term of hydrogen bonding energy predominates during the folding to stabilize protein. The major hydrogen bonding in globular protein occurs between the main-chain N-H and C=O groups, which are the key building blocks of both α-helix and β-sheet structures. Knowledge of such hydrogen bonding networks and the local electrostatics in proteins is essential for proper thermodynamic modeling, prediction of protein folding pathways and binding interactions. Research in the area of protein charge density analysis has recently been stimulated particularly with the interest in the topological analysis of hydrogen bonds, protein-ligand interactions and their electrostatics.[2] Such analyses are performed based on electron density database transfer approach, thanks to ELMAM-2 database. Many more such studies on variety of protein systems might allow researchers to understand the properties of hydrogen bonds better and help characterizing them as done so in small molecule systems. In this line, based on ELMAM-2 database we have modelled charge densities of several high-resolution X-ray protein structures as deposited in the Protein Data Bank. In this presentation we will discuss the topological properties of N-H•••O=C hydrogen bonds present both in the α-helices and β-sheets and estimate their electrostatic interaction energies. Further, efforts will be made to provide a qualitative and quantitative picture of protein-ligand interactions from Hirshfeld surface approach and quantum kernel energy method,[3] respectively and correlate the findings with those obtained from charge density analysis approach.

Amyloidogenic diseases, such as, Alzheimer&#x27;s are caused by adsorption and aggregation of partially unfolded proteins. Adsorption of proteins is a concern in design of biomedical devices, such as dialysis membranes. Protein adsorption is often accompanied by ...

Countless times the students of the Department of General Linguistics, Faculty of Arts, Palacký University have constructed grammars from a semantic basis, performed complex analyses of the communication process and text, and designed process grammars. Professor Kořenský has been the soul and genius of the department since its establishment. Students were equally afraid of his exams as they admired his charm, elegance, wit, and the art of lecturing. The professor's voice will never again be heard in lecture halls and classrooms; language games will never be the same. But the silence and emptiness are easily filled with a warm feeling from the memories of seminars, debates, amusing stories that the professor loved to tell, his magical mischievous smile and the eternal sparkle in his eyes. Professor Kořenský was editor-in-chief of the journal Linguistic Frontiers in the period 2018-2021. Before that he was editor-in-chief of the journal Czech and Slovak Linguistic Review 2 issued by Palacký University Press for many years (2011-2017). We would like to dedicate a few words in remembrance of his genius for the readers of Linguistic Frontiers. We said farewell to our professor Kořenský on the day of 28th of April 2022 in Prague. It was a very sunny and hot spring day. The professor would be happy because he loved to be exposed to the hot touch of the sun and he enjoyed warm walks on hot summer days

This article was written in memory of professor Kořenský, a very prominent personality in Czech linguistics, the founder and former editor in chief of the journal Linguistic Frontiers. The purpose of this paper is to capture essential moments in the life of Professor Kořenský, his achievements and merits in the field of linguistics, and also to describe his unique personality. This article aims to remember this linguistic genius and share these memories with other readers of Linguistic Frontiers.

The PRP2 gene in Saccharomyces cerevisiae encodes an RNA-dependent ATPase that activates spliceosomes for the first transesterification reaction in pre-mRNA splicing. We have identified a mutation in the elongation methionine tRNA gene EMT1 as a dominant, allele-specific suppressor of the temperature-sensitive prp2-1 mutation. The EMT1-201 mutant suppressed prp2-1 by relieving the splicing block at high temperature. Furthermore, EMT1-201 single mutant cells displayed pre-mRNA splicing and cold-sensitive growth defects at 18°. The mutation in EMT1-201 is located in the anticodon, changing CAT to CAG, which presumably allowed EMT1-201 suppressor tRNA to recognize CUG leucine codons instead of AUG methionine codons. Interestingly, the prp2-1 allele contains a point mutation that changes glycine to aspartate, indicating that EMT1-201 does not act by classical missense suppression. Extra copies of the tRNALeu(UAG) gene rescued the cold sensitivity and in vitro splicing defect of EMT1-201...

Biogenesis of eukaryotic tRNAs requires transcription by RNA polymerase III and subsequent processing. 5′ processing of precursor tRNA occurs by a single mechanism, cleavage by RNase P, and usually occurs before 3′ processing although some conditions allow observation of the 3′-first pathway. 3′ processing is relatively complex and is the focus of this review. Precursor RNA 3′ end formation begins with pol III termination generating a variable length 3′ oligo(U) tract that represents an underappreciated and previously unreviewed determinant of processing. Evidence that the pol III-intrinsic 3′ exonuclease activity mediated by Rpc11p affects 3′ oligo(U) length is reviewed. In addition to multiple 3′ nucleases, pre-tRNA processing involves La and Lsm, distinct oligo(U)-binding proteins with proposed chaperone activities. 3′ processing is performed by the endonuclease RNase Z or the exonuclease Rex1p (possibly others) along alternate pathways conditional on La. We review a S. pombe tRNA reporter system that has been used to distinguish two chaperone activities of La protein to its two conserved RNA binding motifs. Pre-tRNAs with structural impairments are degraded by a nuclear surveillance system that mediates polyadenylation by the TRAMP complex followed by 3′ digestion by the nuclear exosome which appears to compete with 3′ processing. We also try to reconcile limited data on pre-tRNA processing and Lsm proteins which largely affects precursors but not mature tRNAs. A pathway is proposed in which 3′ oligo(U) length is a primary determinant of La binding with subsequent steps distinguished by 3′ endo-vs. exo-nucleases, chaperone activities and nuclear surveillance.

If cerebrospinal and interstitial fluids move through very narrow brain flow channels, these restrictive surroundings generate varying levels of fluid shear and different shear rates, and dissolved amyloid monomers absorb different shear energies. It is proposed that dissolved amyloid-␤ protein (A␤) and other amyloid monomers undergo shear-induced conformational changes that ultimately lead to amyloid monomer aggregation even at very low brain flow and shear rates. Soluble A␤ oligomers taken from diseased brains initiate in vivo amyloid formation in non-diseased brains. The brain environment is apparently responsible for this result. A mechanism involving extensional shear is proposed for the formation of a seed A␤ monomer molecule that ultimately promotes templated conformational change of other A␤ molecules. Under non-quiescent, non-equilibrium conditions, gentle extensional shear within the brain parenchyma, and perhaps even during laboratory preparation of A␤ samples, may be sufficient to cause subtle conformational changes in these monomers. These result from brain processes that significantly lower the high activation energy predicted for the quiescent A␤ dimerization process. It is further suggested that changes in brain location and changes brought about by aging expose A␤ molecules to different shear rates, total shear, and types of shear, resulting in different conformational changes in these molecules. The consequences of such changes caused by variable shear energy are proposed to underlie formation of amyloid strains causing different amyloid diseases. Amyloid researchers are urged to undertake studies with amyloids, anti-amyloid drugs, and antibodies while all of these are under shear conditions similar to those in the brain.

Irreversible thermodynamics of single-molecule experiments subject to external constraining forces of a mechanical nature is presented. Extending Onsager's formalism to the non-linear case of systems under non-equilibrium external constraints, we are able to calculate the entropy production and the general non-linear kinetic equations for the variables involved. In particular, we analyze the case of RNA stretching protocols obtaining critical oscillations between different configurational states when forced by external means to remain in the unstable region of its free-energy landscape, as observed in experiments. We also calculate the entropy produced during these hopping events, and show how resonant phenomena in stretching experiments of single RNA macromolecules may arise. We also calculate the hopping rates using Kramer's approach obtaining a good comparison with experiments.

Early events of protein folding can be studied with fast perturbation techniques triggering non-equilibrium relaxation dynamics. A nanosecond laser-excited pH-jump or temperature-jump (T-jump) was applied to initiate helix folding or unfolding of poly-l-glutamic acid (PGA). PGA is a homopolypeptide with titratable carboxyl side-chains whose protonation degree determines the PGA conformation. A pH-jump was realized by the photochemical release of protons and induces PGA folding due to protonation of the side-chains. Otherwise, the helical conformation can be unfolded by a T-jump. We operated under conditions where PGA does not aggregate and temperature and pH are the regulatory properties of its conformation. The experiments were performed in such a manner that the folding/unfolding jump proceeded to the same PGA conformation. We quantified the increase/decrease in helicity induced by the pH-/T-jump and demonstrated that the T-jump results in a relatively small change in helical cont...

Background: Two opposite views have been advanced for the packing of sidechains in globular proteins. The first is the jigsaw puzzle model, in which the complementarity of size and shape is essential. The second, the nuts-andbolts model, suggests that constraints induced by steric complementarity or pairwise specificity have little influence. Here, the angular distributions of sidechains around amino acids of different types are analyzed, in order to capture the preferred (if any) coordination loci in the neighborhood of a given type of amino acid. Results: Some residue pairs select specific coordination states with probabilities about ten times higher than expected for random distributions. This selectivity becomes more pronounced at closer separations leading to an effective free energy of stabilization as large as-2 RT for some sidechain pairs. A list of the most probable coordination sites around each residue type is presented, along with their statistical weights. Conclusions: These data provide guidance as to how to pack selectively the nonbonded sidechains in the neighborhood of a central residue for computer generation of unknown protein structures.

Protein conformations are generated with a noninteracting globule-coil model in which each residue is assumed to take only the native or random-coil state, and a protein conformation is regarded to consist of alternating regions of random coil and globules of native conformation. Statistical weights are taken to have two parts, corresponding to intraresidue and interresidue interactions. The intraresidue statistical weight for a residue in its native state is assumed to be proportional to the empirical frequency of the native (&$), from tabulated statistics. Interresidue energies are taken to be proportional to the number of contacts within each native region. The principal adjustable parameter is the contact energy per contact pair. Proteins studied include trypsin inhibitor, ribonuclease A, lysozyme, and apomyoglobin. The number of native residues is employed as a simple one-dimensional representation of the folding-unfolding coordinate to describe probable folding pathways. When conformations are considered at each point on this coordinate, it is possible to obtain detailed descriptions of the conformational characteristics of relatively rare intermediates along the folding pathway. This technique of "trapping" conformational in-'From the Laboratory of Mathematical Biology, Building IO, Room 4B-56, DCBD

The folding mechanism and dynamics of a helical protein may strongly depend on how quickly its constituent R-helices can fold independently. Thus, our understanding of the protein folding problem may be greatly enhanced by a systematic survey of the folding rates of individual R-helical segments derived from their parent proteins. As a first step, we have studied the relaxation kinetics of the central helix (L9:41-74) of the ribosomal protein L9 from the bacterium Bacillus stearothermophilus, in response to a temperature-jump (T-jump) using infrared spectroscopy. L9:41-74 has been shown to exhibit unusually high helicity in aqueous solution due to a series of side chain-side chain interactions, most of which are electrostatic in nature, while still remaining monomeric over a wide concentration range. Thus, this peptide represents an excellent model system not only for examining how the folding rate of naturally occurring helices differs from that of the widely studied alanine-based peptides, but also for estimating the folding speed limit of (small) helical proteins. Our results show that the T-jump induced relaxation rate of L9:41-74 is significantly slower than that of alanine-based peptides. For example, at 11°C its relaxation time constant is about 2 µs, roughly seven times slower than that of SPE 5 , an alanine-rich peptide of similar chain length. In addition, our results show that the folding rate of a truncated version of L9:41-74 is even slower. Taken together, these results suggest that individual R-helical segments in proteins may fold on a time scale that is significantly slower than the folding time of alanine-based peptides. Furthermore, we argue that the relaxation rate of L9:41-74 measured between 8 and 45°C provides a realistic estimate of the ultimate folding rate of (small) helical proteins over this temperature range.

We compare folding trajectories of chymotrypsin inhibitor (CI2) using a dynamic Monte Carlo scheme with Go-type potentials. The model considers the four backbone atoms of each residue and a sphere centered around C b the diameter of which is chosen according to the type of the side group. Bond lengths and bond angles are kept fixed. Folding trajectories are obtained by giving random increments to the u and w torsion angles with some bias toward the native state. Excluded volume effects are considered. Two sets of 20 trajectories are obtained, with different initial configurations. The first set is generated from random initial configurations. The initial configurations of the second set are generated according to knowledge-based neighbor dependent torsion probabilities derived from triplets in the Protein Data Bank. Compared to chains with randomly generated initial configurations, those generated with neighbor-dependent probabilities (i) fold faster, (ii) have better defined secondary structure elements, and (iii) have less number of non-native contacts during folding. V

An approach to predicting folding nuclei in globular proteins with known three-dimensional structures is proposed. This approach is based on the pinpointing of the lowest saddle points on the barrier between the unfolded state and native structure on the free-energy landscape of a protein chain; the proposed technique uses the dynamic programming method. A comparison of calculation results with experimental data on the folding nuclei of 21 proteins shows that the model provides good Φ value predictions for protein structures determined by X-ray analysis and, less successfully, in structures determined by nuclear magnetic resonance. Consideration of the whole ensemble of transition states provides a better prediction of folding nuclei than consideration of only transition states with lowest free energies. In addition, we predict the location of folding nuclei in three-dimensional structures of some proteins whose folding kinetics is being studied, but there is no experimental evidence concerning their folding nuclei.

A theoretical study has shown that the occurrence of various structural elements in stable folds of random copolymers is exponentially dependent o n the own energy of the element. A similar occurrence-on-energy dependence is observed in globular proteins' from the level of amino acid conformations to the level of overall architectures. Thus, the structural features stabilized by many random sequences are typical of globular proteins while the features rarely observed in proteins are those which are stabilized by only a minor part of the random sequences.

In this paper, an improved Simulated Annealing algorithm for Protein Fold- ing Problem (PFP) is presented. This algorithm called Cluster Perturbation Simulated Annealing (CPSA) is based on a brand new scheme to generate new solutions using a cluster perturbation. The algorithm is divided into two phases: Cluster Perturbation Phase and the Reheat Phase. The first phase obtains a good solution in a small amount of time, and it is applied at very high temperatures. The second phase starts with a threshold temperature and reheats the system for a better exploration. CPSA reduces the execution time of the Simulated Annealing Algorithm without sacrificing quality to find a native structure in PFP in Ab-Initio approaches.

In this paper, Golden Ratio Simulated Annealing (GRSA) for Protein Folding Problem (PFP) is presented. GRSA is similar to Multiquenching Annealing (MQA) and Threshold Temperature Simulated Annealing (TTSA) algorithms. In contrast to MQA and TTSA, GRSA uses several strategies in order to reduce the execution time for finding the best solution of PFP. Firstly, temperature parameters are tuned with an analytical-experimental approach; secondly, a heuristic technique for dividing the search space is implemented. GRSA has a special phase which detects the thermal equilibrium by a least squares method. In addition, a reheat strategy to escape from local optima is applied.

The apparent K,,, for two S. pombe tRNA precursors derived from the supSI and sup3-e tRNAScr genes is 20 nM; the apparent V,, is 2.5 nM/min (supS1) and 1.1 nM/min (supjl-e). Processing studies with precursors of other mutants show that the structures of the acceptor stem and anticodon/intron loop of tRNA are crucial for S. pombe RNase P action.

Mezimolekulové interakce v proteinech - Abstrakt Mgr. Jiří Kysilka Nekovalentní interakce jsou zodpovědné za folding proteinů i za molekulární rozpoznávání během interakce proteinů s dalšími molekulami, například s různými ligandy, dalšími proteiny či molekulami solventu. Abychom těmto procesům, kterých se proteiny účastní, mohli porozumět, je třeba kvalitního popisu nekovalentních interakcí. Většina metod, které jsou výpočetně dostupné pro biologicky zajímavé systémy, však má problém se správným popisem disperzního členu. V této práci je využito korekční schéma DFT/CC pro výpočet interakčních energií malých molekul interagujících s grafitickým povrchem. Tyto výsledky slouží jako benchmark pro interakci funkčních skupin proteinů s hydrofobním prostředím. V následující části práce je zkoumána role nekovalentních interakcí při procesech protein-protein interakce a hydratace proteinu. Na souboru 69 proteinových dimerů byly lokalizovány interakční interface a bylo charakterizováno jejic...

Protein folding has been one of the most difficult problems for over a half-century,Therandom thermal motions causing conformational changes that lead energeticallydownhill towards the native structure, a principle captured in funnel-shaped energylandscapes.Unfolded polypeptides have a wide range of possible conformations. Thesearch problem becomes intractable for classical computers due to the exponentialgrowth of potential conformations with chain length. So far, there is theoretical andexperimental evidence that solving such optimization problems using QuantumComputing approaches such as Quantum Annealing, VQE, and QAOA has anadvantage. Although Google&#39;s DeepMind-AlphaFold has accomplished much,But wecan go even further with the quantum approach.Here we show how to predict structureof protein as well as RNA folding using the Variational Quantum Eigensolver withConditional Value at Risk (CVaR) expectation values for the solution of the problem andfor finding the minimum config...

Protein folding has been one of the most difficult problems for over a half-century,The random thermal motions causing conformational changes that lead energetically downhill towards the native structure, a principle captured in funnel-shaped energy landscapes.Unfolded polypeptides have a wide range of possible conformations. The search problem becomes intractable for classical computers due to the exponential growth of potential conformations with chain length. So far, there is theoretical and experimental evidence that solving such optimization problems using Quantum Computing approaches such as Quantum Annealing, VQE, and QAOA has an advantage. Although Google's DeepMind-AlphaFold has accomplished much,But we can go even further with the quantum approach.Here we show how to predict structure of protein as well as RNA folding using the Variational Quantum Eigensolver with Conditional Value at Risk (CVaR) expectation values for the solution of the problem and for finding the minimum configuration energy and our task is to identify a protein's minimal energy structure. The protein's structure is optimized to reduce energy. Also making sure that all physical constraints are met and encoding the protein folding problem into a qubit operator.

Background: Hepatocellular carcinoma (HCC) is the six most common cancer and the fourth leading cause of cancer-related death worldwide. Recent reports have suggested increasing prevalence of HCC without evidence of hepatitis B and C infection (non-viral HCC). This study aimed to describe the distribution of viral and non-viral risk causes of hepatocellular carcinoma cases at Arifin Achmad General Hospital (AAGH). Methods: This study using a cross-sectional approach conducted at Arifin Achmad General Hospital (AAGH), Riau Province from 2013 to 2017. Data were obtained from medical records of HCC patients using total sampling method. Results: We included 129 cases of whom 64 (49.6%) were associated with viral causes, and 65 (50.4%) were non-viral HCC. Bivariate analyses showed that there was no age difference between viral and non-viral HCC patients, but the prevalence of non-viral HCC was significantly higher in females than males (OR: 3.12; 95% CI: 1.2-8.1; p=0.016). In addition, patients with alpha-fetoprotein (AFP) <400 ng/mL were more frequently associated with non-viral HCC compared with those with elevated AFP 400 ng/mL (OR: 3.71; 95% CI: 1.49-9.26; p=0.004). Conclusion: There was an equal distribution of viral and non-viral causes in HCC cases at AAGH, Riau Province during 2013-2017. This suggests changing etiologies of HCC that may impact HCC surveillance.

In the beginning everything was explained in Biochemistry in terms of hydrogen-bonds (HB). Then, the devastating blow, known as the HB-inventory argument came; hydrogen bonding with water molecules compete with intramolecular hydrogen-bonds. As a result, the HBs paradigm fell from grace. The void that was created immediately filled by Kauzmann's idea of hydrophobic (H O ) effect which reigned supreme in biochemical literature for over 50 years (1960-2010). Cracks in the HB-inventory argument on one hand, and doubts about the adequacy of Kauzmann's model for the H O  effect, have led to a comeback of the HBs, along with a host of new hydrophilic (H I ) effects. The H O  effects lost much of its power-which it never really had-in explaining protein folding and protein-protein association. Instead, the more powerful and richer repertoire of H I  effects took over the reins. The H I  interactions also offered simple and straightforward answers to the problems of protein folding, and protein-protein association.