Kinetic and thermodynamic analysis of proteinlike heteropolymers: Monte Carlo histogram technique

Using Monte Carlo dynamics and the Monte Carlo Histogram Method, the simple three-dimensional 27 monomer lattice copolymer is examined in depth. The thermodynamic properties of various sequences are examined contrasting the behavior of good and poor folding sequences. The good (fast folding) sequences have sharp well-defined thermodynamic transitions while the slow folding sequences have broad ones. We find two independent transitions: a collapse transition to compact states and a folding transition from compact states to the native state. The collapse transition is second order-like, while folding is first order. The system is also studied as a function of the energy parameters. In particular, as the average energetic drive toward compactness is reduced, the two transitions approach each other. At zero average drive, collapse and folding occur almost simultaneously; i.e., the chain collapses directly into the native state. At a specific value of this energy drive the folding temperature falls below the glass point, indicating that the chain is now trapped in local minimum. By varying one parameter in this simple model, we obtain a diverse array of behaviors which may be useful in understanding the different folding properties of various proteins.Comment: LaTeX, 16 pages, figures in separate uufile. Requires psfig.sty Minor revision, fixed typo in preprint number (no other changes

Folding Kinetics of Protein Like Heteropolymers

Using a simple three-dimensional lattice copolymer model and Monte Carlo dynamics, we study the collapse and folding of protein-like heteropolymers. The polymers are 27 monomers long and consist of two monomer types. Although these chains are too long for exhaustive enumeration of all conformations, it is possible to enumerate all the maximally compact conformations, which are 3x3x3 cubes. This allows us to select sequences that have a unique global minimum. We then explore the kinetics of collapse and folding and examine what features determine the various rates. The folding time has a plateau over a broad range of temperatures and diverges at both high and low temperatures. The folding time depends on sequence and is related to the amount of energetic frustration in the native state. The collapse times of the chains are sequence independent and are a few orders of magnitude faster than the folding times, indicating a two-phase folding process. Below a certain temperature the chains exhibit glass-like behavior, characterized by a slowing down of time scales and loss of self-averaging behavior. We explicitly define the glass transition temperature (Tg), and by comparing it to the folding temperature (Tf), we find two classes of sequences: good folders with Tf > Tg and non-folders with Tf < Tg.Comment: 23 pages (plus 10 figures included in a seperate file) LaTeX, no local report nu

Diffusive Dynamics of the Reaction Coordinate for Protein Folding Funnels

The quantitative description of model protein folding kinetics using a diffusive collective reaction coordinate is examined. Direct folding kinetics, diffusional coefficients and free energy profiles are determined from Monte Carlo simulations of a 27-mer, 3 letter code lattice model, which corresponds roughly to a small helical protein. Analytic folding calculations, using simple diffusive rate theory, agree extremely well with the full simulation results. Folding in this system is best seen as a diffusive, funnel-like process.Comment: LaTeX 12 pages, figures include

Recent sedimentological onterpretations in the Avalon terrane of the Boston Basin, Massachusetts

The depositional history of the Boston Basin remains somewhat enigmatic and controversial despite nearly over a century of research. Resolution of the basin's geologic history has remained formidable and complex due. In part, to attempts to work within the existing stratigraphy which often carried with it historic interpretations, many of which went uncontested. More importantly however, our knowledge of depositional systems and mechanisms has Increased significantly over this span of time. Reinterpretatlons In light of these advances were not only Inevitable but neccessary. As a consequence of the circumstances described above, our reinvestigation into the depositional history of the Boston Basin succession, principally the Boston Bay Group, has centered on recognizing, measuring, and coding a suite of facies whose textures In many Instances can be closely linked to specific depositional mechanisms responsible for the emplacement of the facies in question. From this facies analysis a preliminary depositional model for the Boston Basin has begun to emerge. It appears that the Boston Basin originated as a rifted successor, or arc-related basin either just prior to the closure of the Cadomlan Ocean or during the opening of Iapetus. The early history of the basin Is marked by the presence of a suite of bimodal volcanics In the form of water-lain tuffs, dikes, sills, and flows, and coarse debris flows. Geochemlcal markers suggest that the basin was In contact with the open ocean very early In its history. The next stage In the evolution of the Boston Basin was marked by the development of a rapidly prograding submarine elope/fan succession. The slope/fan Betting appears to have been characterized by the deposition of ice frontal and/or ice-rafted dlamictons which periodically overloaded the slope Initiating sediment gravity flows which reworked and redistributed sediment downslope. During periods of more equable climate and/or tectonic quiescence, blankets of fine sand and mud were deposited. There Is no evidence of a shelf or shelf-type deposits during this time. The last stage in the evolution of the basin was the appearance of shelf sediments such as quartz and calcareous sands, and muds with abundant organic matter and shelled organisms. There Is also evidence for climatic warming which is suggested to have been brought about by a tectonlcally-forced rise In eustatic sea-level. R&#xC9;SUM&#xC9; L'hlstoire s&#xE9;dlmentalre du Bassln de Boston Bouleve encore quelques enigmes et controversy et, cela, apr&#xE8;s pr&#xE8;s d'un slecle de travaux. Dans une certain mesure, la r&#xE9;solution de l'histoire g&#xE9;ologlque du bassln est demeur&#xE9;e formidable et complexe par suite des tentatlves de travalller au sein de la stratigraphie actuelle qui. elle, comportalt souvent des interpr&#xE8;tations hlstoriques rareaent mises en doute. Or, plus important est le bond en avant saislssant qu'&#xE0; fait notre connalssance des syst&#xE8;mes et mecanlsmes de d&#xE9;p&#xF4;t durant cette p&#xE9;riode. Il devint done non seuleoent inevitable. mala bien n&#xE9;cessaire de r&#xE9;consider&#xE9;r lea conceptions traditionnelles a la lumi&#xE8;re de ces acquis. Pour ce falre, notre reexamen de l'hlstoire s&#xE9;dimentalre de la succession du Bassln de Boston, et surtout du Groupe de Boston Bay, s'est axe sur la reconnaissance, la mesure et le codage d'une suite de faci&#xE8;s dont les textures sont souvent reli&#xE9;es de fa&#xE7;on intime aux mecanismes de d&#xE9;p&#xF4;t distincts responsables de la raise en place d&#xE9;sdits faci&#xE8;s. Cette analyse faclologique commence &#xE0; &#xE9;ngendrer un mod&#xE8;le pr&#xE9;liminaire du d&#xE9;p&#xF4;t dans le Bassln de Boston. Il semble que le Bassin de Boston alt d&#xE9;but&#xE9; sous forme d'un rift successeur ou d'un bassln alli&#xE9; &#xE0; un arc solt juste avant le serrage de l’Oc&#xE9;an Cadomien, solt lors de l’ouverture de L'Iapetus. L'hlstoire du bassin est d'abord marqu&#xE9;e par la pr&#xE9;sence d'une suite de volcanites blmodales sous formes de tufa aquatiques, dykes, filons-couches. coul&#xE9;es et coul&#xE9;es de d&#xE9;bris. Les marqueurs g&#xE9;ochimiques sugg&#xE9;rent que le bassin &#xE9;tait ouvert sur le large des l’amorce de son hlstoire. Le stade suivant dans l’&#xE9;volution du Bassln de Boston fut marque par le d&#xE9;veloppement d'une s&#xE9;quence de pente et cone sous-marlns &#xE0; progradation rapide. L'environnement de pente et cone semble avoir &#xE9;t&#xE9; carsct&#xE9;rise par le d&#xE9;p&#xF4;t de diamictons glaciaires frontaux et/ou supraglaciares qui ont surcharge p&#xE9;riodiquetoent la pente, declencbant alnsi des &#xE9;coulements gravitalres qui ont repris les s&#xE9;diments et les ont redistribue en bas de pente. Les p&#xE9;riodes de climat plus uniforme et/ou de stase tectonique donnerent lieu &#xE0; des &#xE9;pandages de sable fin et de boue. On ne trouv&#xE9; pas trace d'une plate-forme ou de d&#xE9;p&#xF4;ts typiques d'une plate-forme lors de cette p&#xE9;riode. La derniere phase &#xE9;volutive du bassin correspond &#xE0; L’apparltlon de s&#xE9;diments de plate-forme tels que des sables quartzeux et calcaires alnsi que des boues riches en raatiere organique et en organlsmes coquilllers. Certains Indices temoignent d'un rechauffement climatlque que l'on croit du a une &#xE9;levation eustatlque du niveau marin en reponse aux sollicitations de la tectonique. [Traduit par le journal

Dynamics of polymer chain collapse into compact states

Molecular dynamics simulation methods are used to study the folding of polymer chains into packed cubic states. The polymer model, based on a chain of linked sites moving in the continuum, includes both excluded volume and torsional interactions. Different native-state packing arrangements and chain lengths are explored; the organization of the native state is found to affect both the ability of the chain to fold successfully and the nature of the folding pathway as the system is gradually cooled. An order parameter based on contact counts is used to provide information about the folding process, with contacts additionally classified according to criteria such as core and surface sites or local and distant site pairs. Fully detailed contact maps and their evolution are also examined.Comment: 11 pages, 11 figures (some low resolution

Genome-wide mapping of the distribution of CarD, RNAP σA, and RNAP β on the Mycobacterium smegmatis chromosome using chromatin immunoprecipitation sequencing

CarD is an essential mycobacterial protein that binds the RNA polymerase (RNAP) and affects the transcriptional profile of Mycobacterium smegmatis and Mycobacterium tuberculosis [6]. We predicted that CarD was directly regulating RNAP function but our prior experiments had not determined at what stage of transcription CarD was functioning and at which genes CarD interacted with the RNAP. To begin to address these open questions, we performed chromatin immunoprecipitation sequencing (ChIP-seq) to survey the distribution of CarD throughout the M. smegmatis chromosome. The distribution of RNAP subunits β and σA were also profiled. We expected that RNAP β would be present throughout transcribed regions and RNAP σA would be predominantly enriched at promoters based on work in Escherichia coli [3], however this had yet to be determined in mycobacteria. The ChIP-seq analyses revealed that CarD was never present on the genome in the absence of RNAP, was primarily associated with promoter regions, and was highly correlated with the distribution of RNAP σA. The colocalization of σA and CarD led us to propose that in vivo, CarD associates with RNAP initiation complexes at most promoters and is therefore a global regulator of transcription initiation. Here we describe in detail the data from the ChIP-seq experiments associated with the study published by Srivastava and colleagues in the Proceedings of the National Academy of Science in 2013 [5] as well as discuss the findings from this dataset in relation to both CarD and mycobacterial transcription as a whole. The ChIP-seq data have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE48164)