Flexibility Patterns Research Articles

Dynameomics: Large‐scale assessment of native protein flexibility

Structure is only the first step in understanding the interactions and functions of proteins. In this paper, we explore the flexibility of proteins across a broad database of over 250 solvated protein molecular dynamics simulations in water for an aggregate simulation time of approximately 6 micros. These simulations are from our Dynameomics project, and these proteins represent approximately 75% of all known protein structures. We employ principal component analysis of the atomic coordinates over time to determine the primary axis and magnitude of the flexibility of each atom in a simulation. This technique gives us both a database of flexibility for many protein fold families and a compact visual representation of a particular protein's native-state conformational space, neither of which are available using experimental methods alone. These tools allow us to better understand the nature of protein motion and to describe its relationship to other structural and dynamical characteristics. In addition to reporting general properties of protein flexibility and detailing many dynamic motifs, we characterize the relationship between protein native-state flexibility and early events in thermal unfolding and show that flexibility predicts how a protein will begin to unfold. We provide evidence that fold families have conserved flexibility patterns, and family members who deviate from the conserved patterns have very low sequence identity. Finally, we examine novel aspects of highly inflexible loops that are as important to structural integrity as conventional secondary structure. These loops, which are difficult if not impossible to locate without dynamic data, may constitute new structural motifs.

Structural properties of replication origins in yeast DNA sequences

Sequence-dependent DNA flexibility is an important structural property originating from the DNA 3D structure. In this paper, we investigate the DNA flexibility of the budding yeast (S. Cerevisiae) replication origins on a genome-wide scale using flexibility parameters from two different models, the trinucleotide and the tetranucleotide models. Based on analyzing average flexibility profiles of 270 replication origins, we find that yeast replication origins are significantly rigid compared with their surrounding genomic regions. To further understand the highly distinctive property of replication origins, we compare the flexibility patterns between yeast replication origins and promoters, and find that they both contain significantly rigid DNAs. Our results suggest that DNA flexibility is an important factor that helps proteins recognize and bind the target sites in order to initiate DNA replication. Inspired by the role of the rigid region in promoters, we speculate that the rigid replication origins may facilitate binding of proteins, including the origin recognition complex (ORC), Cdc6, Cdt1 and the MCM2-7 complex.

Flexibility of Human Cytochromes P450: Molecular Dynamics Reveals Differences between CYPs 3A4, 2C9, and 2A6, which Correlate with Their Substrate Preferences

Molecular dynamics (MD) simulations at normal and high temperature were used to study the flexibility and malleability of three microsomal cytochromes P450 (CYPs): CYP3A4, CYP2C9, and CYP2A6. Comparison of B-factors (describing the atomic fluctuations) between X-ray and MD data shows that the X-ray B-factors are significantly lower in the regions where the crystal contacts occur than for other regions. Consequently, the conclusions about CYP flexibility based solely on the X-ray data might be misleading. Comparison of flexibility patterns of the three CYPs enabled common features and variations in flexibility and malleability of the studied CYPs to be identified. The previously described pattern of flexibility in topological elements of microsomal CYPs (a rigid heme binding core, a malleable distal side and intermediately flexible proximal side) was confirmed. These topological features provide an important combination of high stereo- and regio-specificity (mediated by the relative rigidity in the neighborhood of the heme), together with high substrate promiscuity due to the more flexible active site and the malleability of the distal side. The data acquired here show that the malleability of the three studied CYPs correlates with their substrate specificity: CYP2A6 has a narrow substrate range and is the most rigid, CYP3A4 is the most promiscuous CYP known and is the most malleable, and CYP2C9 is intermediate in terms of both its substrate specificity and malleability. Thus, the malleability of CYPs is probably a major determinant of their substrate specificity.

One Company, Four Factories: Coordinating Employment Flexibility Practices with Local Trade Unions

This article reports a case study of employment flexibility patterns in four factories of a multinational company in western and central Europe. There is remarkable variation in these patterns, which structural and institutional factors alone do not explain. Rather, the interests of management and local unions, and the character of their mutual interaction, are central for workplace employment practices. In factories with cooperative industrial relations, unions are extensively involved in employment flexibility even if management lacks a legal obligation or economic incentives to do so. In consequence, the company policy is neither a straightforward adaptation to host country institutions, nor a simple diffusion of corporate ‘best practice’.

Aloetismo em Acromyrmex subterraneus brunneus Forel (Hymenoptera, Formicidae), durante o forrageamento, cultivo do jardim de fungo e devolução dos materiais forrageados

Leaf cutting-ants present a sophisticated division of labor during foraging, fungus-garden cultivation and devolution of foraged materials. Material with different degrees of moisture and hardness (floral sponge, polystyrene, plastic and clay) were offered to two Acromyrmex subterraneus brunneus Forel, 1911 laboratory colonies. The different size categories of workers were observed during the execution of 14 subtasks. Relative probability performance and alloethic curves were used to verify behavioral flexibility and behavioral stereotyped patterns in the workers. The behavioral patterns could establish roles within probable subcastes.

The relative flexibility of B-DNA and A-RNA duplexes: database analysis

An extensive analysis of structural databases is carried out to investigate the relative flexibility of B-DNA and A-RNA duplexes in crystal form. Our results show that the general anisotropic concept of flexibility is not very useful to compare the deformability of B-DNA and A-RNA duplexes, since the flexibility patterns of B-DNA and A-RNA are quite different. In other words, 'flexibility' is a dangerous word for describing macromolecules, unless it is clearly defined. A few soft essential movements explain most of the natural flexibility of A-RNA, whereas many are necessary for B-DNA. Essential movements occurring in naked B-DNAs are identical to those necessary to deform DNA in DNA-protein complexes, which suggest that evolution has designed DNA-protein complexes so that B-DNA is deformed according to its natural tendency. DNA is generally more flexible, but for some distortions A-RNA is easier to deform. Local stiffness constants obtained for naked B-DNAs and DNA complexes are very close, demonstrating that global distortions in DNA necessary for binding to proteins are the result of the addition of small concerted deformations at the base-pair level. Finally, it is worth noting that in general the picture of the relative deformability of A-RNA and DNA derived from database analysis agrees very well with that derived from state of the art molecular dynamics (MD) simulations.

Theoretical Study of a New DNA Structure: The Antiparallel Hoogsteen Duplex

The structure of a new form of duplex DNA, the antiparallel Hoogsteen duplex, is studied in polyd(AT) sequences by means of state-of-the-art molecular dynamics simulations in aqueous solution. The structure, which was found to be stable in all of the simulations, has many similarities with the standard Watson-Crick duplex in terms of general structure, flexibility, and molecular recognition patterns. Accurate MM-PB/SA (and MM-GB/SA) analysis shows that the new structure has an effective energy similar to that of the B-type duplex, while it is slightly disfavored by intramolecular entropic considerations. Overall, MD simulations strongly suggest that the antiparallel Hoogsteen duplex is an accessible structure for a polyd(AT) sequence, which might compete under proper experimental conditions with normal B-DNA. MD simulations also suggest that chimeras containing Watson-Crick duplex and Hoogsteen antiparallel helices might coexist in a common structure, but with the differential characteristics of both type of structures preserved.

Predictors of flexibility and pain patterns in thoracolumbar and lumbar idiopathic scoliosis.

A retrospective evaluation of radiographs in patients with idiopathic scoliosis was undertaken to assess predictors of flexibility. To evaluate potential predictors of flexibility in patients with thoracolumbar and lumbar scoliosis. Curve flexibility is an important consideration in the operative management of idiopathic scoliosis. Flexibility of the major curve is a useful predictor of expected surgical correction, and flexibility of compensatory curves determines whether they are structural or nonstructural. An accurate assessment of curve flexibility has important implications on surgical approaches and planning for deformity correction. The role of age and curve magnitude in predicting curve flexibility has not been well defined. A quantitative assessment of changes in curve flexibility with age and progression of deformity may yield important insight into the change in surgical management options over time. A retrospective review of 75 patients with idiopathic thoracolumbar and lumbar scoliosis (age range 13-78 years) was undertaken. Preoperative standing and side-bending radiographs of thoracolumbar and lumbar curves were evaluated. Cobb angles of structural and fractional curves, curve flexibility, presence of lateral listhesis, and axial and radicular pain were documented. Predictors of structural and fractional curve flexibility were evaluated with correlation and regression analysis. Correlation analysis was used to demonstrate an association between radiographic findings and the clinical presentation. Seventy-five patients had an average major curve magnitude of 56 degrees (range 34-82 degrees ) with flexibility averaging 55% (range 20-93%). Structural curve flexibility was highly inversely correlated with both curve magnitude (r = -0.7; P< 0.001) and with age (r = -0.6; P< 0.001). Lumbar fractional curve (L4-S1) flexibility showed a high inverse correlation with age (r = -0.65; P< 0.001) but did not show correlation with Cobb angle. Thoracic compensatory curves showed a moderate correlation with Cobb angle (r = 0.53). Structural and fractional curve flexibility showed high correlation with each other (r = 0.5-0.66). Regression analysis yielded a formula to predict the flexibility of the structural curve (FSC): FSC = 130 - (Cobb + Age/2). Axial pain was correlated with age (r = 0.63); however, it was not correlated with curve magnitude. We have shown that curve magnitude and patient age are the main predictors of structural flexibility. Every 10 degrees increase in curve magnitude over 40 degrees results in a 10% decrease in flexibility; every 10-year increase in age decreases flexibility of the structural curve by 5% and the lumbosacral fractional curve by 10%. Curve magnitude and age of the patients are significant predictors of curve flexibility. The demonstration of this association offers useful information in estimating how surgical options for deformity correction may change over time.

Company labour flexibility strategies in The Netherlands: an institutional perspective

Despite important differences in labour flexibility patterns in different countries and despite clear indications of the important role of institutional factors with respect to HRM, to date there has been little research on the interaction between the institutional context and the HRM of companies. This paper seeks to address this issue with regard to labour flexibility strategies and reveals a promising approach to learning how the development of a topic, such as labour flexibility, takes place in practice. The case of The Netherlands clearly shows the interaction between the institutional context and company flexibility strategies. The institutional context was found to influence company strategies but, in return, these strategies were later seen to impact the institutional setting. In The Netherlands the system of labour relations has been adapted in response to calls from companies for more flexible labour relations. This has led to changes in labour laws and regulations, which, in turn, have stimulated new company strategies.

Flexibility and its effects on sports injury and performance.

Flexibility measures can be static [end of ROM (range of motion)], dynamic-passive (stiffness/compliance) or dynamic-active (muscle contracted, stiffness/compliance). Dynamic measures of flexibility are less dependent on patient discomfort and are more objective. Acute and chronic changes in flexibility are likely to occur with stretching exercises, but it is difficult to distinguish between changes in stretch tolerance as opposed to changes in muscle stiffness. How flexibility is measured impacts these findings. There is no scientifically based prescription for flexibility training and no conclusive statements can be made about the relationship of flexibility to athletic injury. The literature reports opposing findings from different samples, frequently does not distinguish between strain, sprain and overuse injury, and rarely uses the proper denominator of exposure. There is basic scientific evidence to suggest that active warm-up may be protective against muscle strain injury but clinical research is equivocal on this point. Typically, specific flexibility patterns are associated with specific sports and even positions within sports. The relationship of flexibility to athletic performance is likely to be sport-dependent. Decreased flexibility has been associated with increased in-line running and walking economy. Increased stiffness may be associated with increased isometric and concentric force generation, and muscle energy storage may be best manifested by closely matching muscle stiffness to the frequency of movement in stretch-shorten type contractions.

Ankle flexibility and injury patterns in dancers.

Lower-extremity injuries are common among dancers and cause significant absences from rehearsals and performances. For this study of lower-extremity injuries in 101 ballet and 47 modern dance students, injuries requiring medical attention sustained over 1 academic year were associated with the following data obtained at the beginning of the school year: ankle flexibility, sex, dance discipline, previous injury, body mass index, and years of training. Eighty-three of the 148 students (age range, 12 to 28 years) reported prior lower-limb injuries, the most common being ankle sprains (28% of all dancers). Previous leg injuries correlated significantly with lower dorsiflexion measurements and with more new injuries. Female students had greater ankle and first metatarsophalangeal flexibility. Modern dancers had greater ankle inversion. Ninety-four students sustained 177 injuries during the study, including 75 sprains or strains and 71 cases of tendinitis. Thirty-nine percent (N = 69) were ankle injuries; 18% (N = 33) were knee injuries; 23% (N = 40) were foot injuries; and 20% (N = 35) were either hip or thigh injuries. Sixty-seven percent (N = 78) of the injured students were ballet dancers. Age, years of training, body mass index, sex, and ankle range of motion measurement had no predictive value for injury; previous injury and dance discipline both correlated with increased risk of injury.

Flexibility and employment patterns in the contemporary paper industry: a comparative analysis of mills in Britain and Finland

This article examines the model of the flexible firm in eight British and Finnish paper mills. In spite of increasing competition and considerable technological change, there was little evidence of flexibility. The authors conclude that peripheralisation of employment would be disastrous in such a capitally‐intensive environment where employers rely on highly‐skilled, experienced, full‐time workers to operate advanced machinery continuously.

Changing Management Approaches to Employee Relations in Ireland

Numerous management commentators have suggested that the 1980s have witnessed considerable change in employee relations at establishment level in Irish organizations. However, much of this analysis has been quite vague on the precise nature of such change. Employee relations management in Ireland has traditionally been associated with a strong collectivist, industrial relations emphasis. Attempts to evaluate the extent of change in management approaches to employee relations in the 1980s. In particular looks at issues such as developments in employment structure, flexibility and changing patterns of industrial conflict. Also considers the emergence of Human Resource Management (HRM) approaches in the Irish context.

Signals in DNA sequences and their potential properties

DNA and RNA molecules contain signals which are recognized by regulatory proteins or enzymes either directly, through their nucleotide sequences or indirectly, through induced structural changes on their neighboring sequences. To date, most signal searches have been focused on specific recurrences of nucleotide sequences. Much less attention has been directed towards the structure, flexibility and hydrogen-bonding patterns that recognition elements may possess. Here we review the various methods involved in such searches. In particular, however, we also address the searches for potential properties. In this regard it is of interest to inspect the asymmetry in the distributions of complementary oligomers near biological features. Upstream of transcription initiation the frequencies of G-rich oligomers are particularly high (Nussinov, 1987a; 1990). The frequencies of C-rich oligomers are lower. A-tracts are also very frequent in these regions. This may correlate with the recent finding that guanine, but not cytosine, tracts enhance A-tract directed bends (Milton et al., 1990). Presumably A-tracts near G-tracts on the same strand may induce a structural change in the G-tracts which may enhance the bend. G-tracts may have the potential for participating in a DNA bend due to their compression of the major groove. Thus, proteins may not always be necessary to induce DNA conformational changes. This example illustrates the importance of studies of the properties of DNA oligomers in regulatory regions, and of algorithms for their detection.

Lower extremity flexibility patterns in classical ballet dancers and their correlation to lateral hip and knee injuries.

Knee and hip problems account for up to 40% of injuries in classical ballet. Despite apparent flexibility, many dancers appeared to have tight iliotibial bands that contributed to lower limb problems. Thirty senior female ballet dancers were contrasted with thirty age-matched active volunteers for hip and knee range of motion, and the information derived was correlated with their orthopaedic medical histories. Dancers spent a reasonable period of time warming up, but it was usually with an unbalanced routine that emphasized hip abduction and external rotation to the exclusion of adduction work. This was reflected in the significantly lower range of passive hip adduction and internal rotation compared to the controls. Furthermore, the older and more experienced the dancer, the more this trend was exaggerated. This unbalanced flexibility may play a role in the production of lateral knee pain (30% of the dancers) and anterior hip pain (33% of the dancers). It is suggested that more attention should be given to a balanced stretching regimen as part of the dancers' warmup in an effort to reduce the frequency of some of the chronic hip and knee complaints.