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1.
Principles of protein folding--a perspective from simple exact models.   总被引:32,自引:12,他引:20       下载免费PDF全文
General principles of protein structure, stability, and folding kinetics have recently been explored in computer simulations of simple exact lattice models. These models represent protein chains at a rudimentary level, but they involve few parameters, approximations, or implicit biases, and they allow complete explorations of conformational and sequence spaces. Such simulations have resulted in testable predictions that are sometimes unanticipated: The folding code is mainly binary and delocalized throughout the amino acid sequence. The secondary and tertiary structures of a protein are specified mainly by the sequence of polar and nonpolar monomers. More specific interactions may refine the structure, rather than dominate the folding code. Simple exact models can account for the properties that characterize protein folding: two-state cooperativity, secondary and tertiary structures, and multistage folding kinetics--fast hydrophobic collapse followed by slower annealing. These studies suggest the possibility of creating "foldable" chain molecules other than proteins. The encoding of a unique compact chain conformation may not require amino acids; it may require only the ability to synthesize specific monomer sequences in which at least one monomer type is solvent-averse.  相似文献   
2.
Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000) of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through meta-analysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford.edu/) which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples.  相似文献   
3.
Summary The mitochondrial outer membrane contains voltagegated channels called VDAC that are responsible for the flux of metabolic substrates and metal ions across this membrane. The addition of micromolar quantities of aluminum chloride to phospholipid membranes containing VDAC channels greatly inhibits the voltage dependence of the channels' permeability. The channels remain in their high conducting (open) state even at high membrane potentials. An analysis of the change in the voltage-dependence parameters revealed that the steepness of the voltage dependence decreased while the voltage needed to close half the channels increased. The energy difference between the open and closed states in the absence of an applied potential did not change. Therefore, the results are consistent with aluminum neutralizing the voltage sensor of the channel. pH shift experiments showed that positively charged aluminum species in solution were not involved. The active form was identified as being either (or both) the aluminum hydroxide or the tetrahydroxoaluminate form. Both of these could reasonably be expected to neutralize a positively charged voltage sensor. Aluminum had no detectable effect of either single-channel conductance or selectivity, indicating that the sensor is probably not located in the channel proper and is distinct from the selectivity filter.  相似文献   
4.
Hydrogen bonding in globular proteins.   总被引:17,自引:0,他引:17  
A global census of the hydrogen bonds in 42 X-ray-elucidated proteins was taken and the following demographic trends identified: (1) Most hydrogen bonds are local, i.e. between partners that are close in sequence, the primary exception being hydrogen-bonded ion pairs. (2) Most hydrogen bonds are between backbone atoms in the protein, an average of 68%. (3) All proteins studied have extensive hydrogen-bonded secondary structure, an average of 82%. (4) Almost all backbone hydrogen bonds are within single elements of secondary structure. An approximate rule of thirds applies: slightly more than one-third (37%) form i----i--3 hydrogen bonds, almost one-third (32%) form i----i--4 hydrogen bonds, and slightly less than one-third (26%) reside in paired strands of beta-sheet. The remaining 5% are not wholly within an individual helix, turn or sheet. (5) Side-chain to backbone hydrogen bonds are clustered at helix-capping positions. (6) An extensive network of hydrogen bonds is present in helices. (7) To a close approximation, the total number of hydrogen bonds is a simple function of a protein's helix and sheet content. (8) A unique quantity, termed the reduced number of hydrogen bonds, is defined as the maximum number of hydrogen bonds possible when every donor:acceptor pair is constrained to be 1:1. This quantity scales linearly with chain length, with 0.71 reduced hydrogen bond per residue. Implications of these results for pathways of protein folding are discussed.  相似文献   
5.
6.
The polychaete worm Serpula vermicularis (Serpulidae) filterfeeds at the mouth of its calcareous tube, but retreats intothe tube when startled by mechanical stimuli likely to be associatedwith predators. While in its tube, a worm is safe but cannotfeed. Thus, hiding has a lost-opportunity cost. We show thatthis cost can be substantial, given that food in the naturalhabitat appears in pulses, and good feeding conditions may notlast long or recur frequently. We expect that a worm's hidingtime will be sensitive to the lost-opportunity cost, and wepresent data from a series of experiments that support thisprediction. The worms seem able to track relatively short-termchanges in food availability, and some evidence suggests thatthey assess food availability on a relative basis, comparingcurrent feeding conditions to those recently experienced. Hidingand other types of cryptic behavior are common antipredatortactics, and animals may commonly adjust the durations of suchbehaviors to current benefits and costs (including lost opportunity),as they perceive them  相似文献   
7.
Collagenase inhibitors retarding invasion of a human tumor in nude mice   总被引:3,自引:0,他引:3  
Tumor invasion has been correlated with the ability of tumor cells to produce collagenolytic enzymes which are capable of degrading normal host tissues. However, the human small cell carcinoma implanted subcutanouesly and growing progressively in athymic (nude) mice produced large quantities of collagenase but did not appear to significantly infultrate adjacent host tissue. In comparison, subcutaneously implanted murine Lewis lung tumors produced similar quantities of collagenase and were locally invasive. The human tumors were surrounded by a compact layer of fibroblast cells in a fibrous matrix. This fibrous sheath exhibited anticollagenase activity and indicated a mechanism of host tissue resistance to invasion via the formation of inhibitors to degradative enzymes produced by tumor cells.  相似文献   
8.
Invariance of object recognition to translation in the visual field is a fundamental property of human pattern vision. In three experiments we investigated this capability by training subjects to distinguish between random checkerboard stimuli. We show that the improvement of discrimination performance does not transfer across the visual field if learning is restricted to a particular location in the retinal image. Accuracy after retinal translation shows no sign of decay over time and remains at the same level it had at the beginning of the training. It is suggested that in two-dimensional translation invariance-as in three-dimensional rotation invariance-the human visual system is relying on memory-intensive rather than computation-intensive processes. Multiple position- and stimulus-specific learning events may be required before recognition is independent of retinal location.  相似文献   
9.
We describe a new computer algorithm for finding low-energy conformations of proteins. It is a chain-growth method that uses a heuristic bias function to help assemble a hydrophobic core. We call it the Core-directed chain Growth method (CG). We test the CG method on several well-known literature examples of HP lattice model proteins [in which proteins are modeled as sequences of hydrophobic (H) and polar (P) monomers], ranging from 20-64 monomers in two dimensions, and up to 88-mers in three dimensions. Previous nonexhaustive methods--Monte Carlo, a Genetic Algorithm, Hydrophobic Zippers, and Contact Interactions--have been tried on these same model sequences. CG is substantially better at finding the global optima, and avoiding local optima, and it does so in comparable or shorter times. CG finds the global minimum energy of the longest HP lattice model chain for which the global optimum is known, a 3D 88-mer that has only been reachable before by the CHCC complete search method. CG has the potential advantage that it should have nonexponential scaling with chain length. We believe this is a promising method for conformational searching in protein folding algorithms.  相似文献   
10.
The objective of the study reported here was to investigate three factors that may affect the amounts of water consumed and urine excreted by a rat in the metabolism cage: water dilution, housing, and food. Young F344/N rats (eight per group) were used for all experiments. Food was withheld from rats before each 16-h urine collection, then rats were transferred into a metabolism cage. For trial A (water dilution), urine was collected from rats supplied with dyed water (0.05%, vol/vol). This was repeated three times over a 2-week period. Dye in water or urine was quantified, using a spectrophotometer. For trial B (housing), rats were individually housed in wire cages for 3 weeks before the first urine collection. Then they were group housed in the solid-bottom cage (four per cage). After 2 weeks of acclimation, urine collection was repeated. For trial C (food), one group of rats was provided with food, the other was not, during urine collection. About 8% of urine samples of small volume (< or = 3 ml) from trial A were contaminated with drinking water up to 13% of volume. The average urine volume associated with individual housing was approximately twice as large as that associated with group housing. When food was provided during urine collection, rats consumed similar amounts of water but excreted significantly smaller amounts of urine than did rats without food. It was concluded that water dilution of a urine sample from a sipper bottle is relatively small; rats individually housed in wire caging before urine collection can consume and excrete a larger quantity of water, compared with rats group housed in solid-bottom cages; and highly variable urine volumes are, in part, associated with lack of access to food during urine collection.  相似文献   
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