Anharmonicity and self-similarity of the free energy landscape of protein G

The near-native free energy landscape of protein G is investigated through 0.4 microseconds-long atomistic molecular dynamics simulations in explicit solvent. A theoretical and computational framework is used to assess the time-dependence of salient thermodynamical features. While the quasi-harmonic character of the free energy is found to degrade in a few ns, the slow modes display a very mild dependence on the trajectory duration. This property originates from a striking self-similarity of the free energy landscape embodied by the consistency of the principal directions of the local minima, where the system dwells for several ns, and of the virtual jumps connecting them.Comment: revtex, 6 pages, 5 figure

Statistical Properties of Contact Maps

A contact map is a simple representation of the structure of proteins and other chain-like macromolecules. This representation is quite amenable to numerical studies of folding. We show that the number of contact maps corresponding to the possible configurations of a polypeptide chain of N amino acids, represented by (N-1)-step self avoiding walks on a lattice, grows exponentially with N for all dimensions D>1. We carry out exact enumerations in D=2 on the square and triangular lattices for walks of up to 20 steps and investigate various statistical properties of contact maps corresponding to such walks. We also study the exact statistics of contact maps generated by walks on a ladder.Comment: Latex file, 15 pages, 12 eps figures. To appear on Phys. Rev.

DESIGNING ENTREPRENEURIAL BUSINESS MODEL IN THE IRANIAN CLUB INDUSTRY IN POST-CORONAVIRUS CONDITIONS

The purpose of this study was to investigate the COVID-19 and the challenges facing the club industry in developing countries. In this qualitative-analytical study, 17 sports experts, sports club managers, and sports entrepreneurs were interviewed based on purposive and triangular sampling methods. The data analysis was also performed by open and axial coding, of which 6 concepts and 42 categories were classified under 6 general themes. The main concepts include government support, financial issues, club activity, sponsorship, mental consequences, and social media. This study highlights the role of sports entrepreneurship in overcoming problems. Managers must use the ability of entrepreneurship because entrepreneurship is considered essential in the economy and provides the impetus for economic growth. Sports entrepreneurship can overcome the coronavirus crisis and solve the problems that have arisen

在后冠状病毒（COVID-19）环境下的伊朗健身俱乐部行业发展创业商业模式

The purpose of this study was to investigate the COVID-19 and the challenges facing the club industry in developing countries. In this qualitative-analytical study, 17 sports experts, sports club managers, and sports entrepreneurs were interviewed based on purposive and triangular sampling methods. The data analysis was also performed by open and axial coding, of which 6 concepts and 42 categories were classified under 6 general themes. The main concepts include government support, financial issues, club activity, sponsorship, mental consequences, and social media. This study highlights the role of sports entrepreneurship in overcoming problems. Managers must use the ability of entrepreneurship because entrepreneurship is considered essential in the economy and provides the impetus for economic growth. Sports entrepreneurship can overcome the coronavirus crisis and solve the problems that have arisen.Целью настоящего исследования было изучить COVID-19 и проблемы, стоящие перед клубной индустрией в развивающихся странах. В этом качественно-аналитическом исследовании были опрошены 17 спортивных экспертов, менеджеров спортивных клубов и предпринимателей в области спорта на основе методов целевой и трехчастной выборки. Анализ данных также проводился с помощью открытого и осевого кодирования; 6 подходов и 42 категории были классифицированы по шести общим темам: государственная поддержка, финансовые вопросы, деятельность клубов, спонсорство, психологические последствия и социальные сети. В работе подчеркивается роль предпринимательства в спортивной индустрии в преодолении проблем. Менеджеры должны использовать способность к предпринимательству, поскольку оно дает импульс для экономического роста. Предпринимательство в спортивной индустрии может преодолеть кризис как последствие коронавируса и решить возникшие проблемы.本研究的目的是探讨发展中国家的健身俱乐部行业面临的与COVID-19有关的挑战。在这项定性与分析研究中，基于目的性和三部分抽样法，采访了17位体育专家、体育俱乐部经理和体育企业家。数据分析也采用了开放式和主轴性编码的方式进行：6种方法和42个类别被划分了为6个共同主题。关键概念包括：政府支持、财务问题、俱乐部活动、赞助、心理健康影响和社会网络。这项研究强调了体育企业家精神在克服问题方面的作用。管理者应该利用创业的能力，因为它对经济很重要，能推动经济增长。体育创业将有助于克服冠状病毒影响等危机，解决经济中出现的问题

Mutation analysis of KRAS and BRAF genes in metastatic colorectal cancer: A first large scale study from Iran

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. Materials and Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. Results: KRAS mutations were present in 33.6 cases (n=336). Of KRAS mutation positive cases, 85.1 were in codon 12 and 14.9 were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable

Long-range correlation and multifractality in Bach's Inventions pitches

We show that it can be considered some of Bach pitches series as a stochastic process with scaling behavior. Using multifractal deterend fluctuation analysis (MF-DFA) method, frequency series of Bach pitches have been analyzed. In this view we find same second moment exponents (after double profiling) in ranges (1.7-1.8) in his works. Comparing MF-DFA results of original series to those for shuffled and surrogate series we can distinguish multifractality due to long-range correlations and a broad probability density function. Finally we determine the scaling exponents and singularity spectrum. We conclude fat tail has more effect in its multifractality nature than long-range correlations.Comment: 18 page, 6 figures, to appear in JSTA

Low-Cost High-Throughput Genotyping for Diagnosing Familial Hypercholesterolemia

BACKGROUND: Familial hypercholesterolemia (FH) is a common but underdiagnosed genetic disorder characterized by high low-density lipoprotein cholesterol levels and premature cardiovascular disease. Current sequencing methods to diagnose FH are expensive and time-consuming. In this study, we evaluated the accuracy of a low-cost, high-throughput genotyping array for diagnosing FH. METHODS: An Illumina Global Screening Array was customized to include probes for 636 variants, previously classified as FH-causing variants. First, its theoretical coverage was assessed in all FH variant carriers diagnosed through next-generation sequencing between 2016 and 2022 in the Netherlands (n=1772). Next, the performance of the array was validated in another sample of FH variant carriers previously identified in the Dutch FH cascade screening program (n=1268). RESULTS: The theoretical coverage of the array for FH-causing variants was 91.3%. Validation of the array was assessed in a sample of 1268 carriers of whom 1015 carried a variant in LDLR, 250 in APOB, and 3 in PCSK9. The overall sensitivity was 94.7% and increased to 98.2% after excluding participants with variants not included in the array design. Copy number variation analysis yielded a 89.4% sensitivity. In 18 carriers, the array identified a total of 19 additional FH-causing variants. Subsequent DNA analysis confirmed 5 of the additionally identified variants, yielding a false-positive result in 16 subjects (1.3%).CONCLUSIONS: The FH genotyping array is a promising tool for genetically diagnosing FH at low costs and has the potential to greatly increase accessibility to genetic testing for FH. Continuous customization of the array will further improve its performance.</p

Resistance distance, information centrality, node vulnerability and vibrations in complex networks

We discuss three seemingly unrelated quantities that have been introduced in different fields of science for complex networks. The three quantities are the resistance distance, the information centrality and the node displacement. We first prove various relations among them. Then we focus on the node displacement, showing its usefulness as an index of node vulnerability.We argue that the node displacement has a better resolution as a measure of node vulnerability than the degree and the information centrality

Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles

The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society