Since the goal of this step is to identify double-stranded DNAs for DNA sequence comparison, we developed a simple approach for detecting base pairs by using two distance measures: "H-distance" and "stagger distance". A base-pair is defined between two bases when both the maximum H-distance and the maximum stagger distance are less than their respective cutoff values.
If a base has more than one potential pairing partner, the one with the smallest stagger distance will be chosen. Using a heuristic approach, we found that a combination of an H-distance cutoff of 4. A double-stranded DNA is then defined as a group of polynucleotide chains that are canonically joined by base-pairing for example, a holiday junction is not considered as a double-stranded DNA.
We developed an empirical method to detect such a "crack" in a DNA backbone: when one or more sequential nucleotides are missing in one strand of a double-stranded DNA, the distance between the C 1 ' atoms of the nucleotides flanking the break or missing region is calculated. Most of the cracks detected by this criterion were related to DNA modification and replication data not shown.
Protein-DNA complexes with special features. A DNA base is considered to be in contact with a protein if the distance between any heavy atom of the base and any heavy atom of the protein is less than a cutoff value the default cutoff is 4.
When the distances between both the major and minor groove atoms of a base and a protein atom are within the cutoff value, the type of the base-protein contact is determined by comparing the contact distances and the angle formed by the "major groove atom"-"protein atom"-"minor groove atom". If the angle is less than 40 degrees, the contact with the longer distance is considered to be shielded by the shorter contact and is thus discarded.
We use several measures to describe the nature of protein-DNA interactions: 1 major minor groove contact number refers to the number of major minor groove DNA bases that are in contact with protein; 2 major groove contact ratio is calculated as the ratio between the number of major groove contacts and the sum of major and minor groove contacts; 3 base backbone contact number refers to the number of nucleotides whose base backbone is in contact with protein; 4 base contact ratio is calculated as the ratio between the number of base contacts and the sum of base and backbone contacts.
Comparison of such complexes can be problematic as these complexes have different protein-DNA binding entities. To resolve such a problem, we use a new term "protein-DNA binding unit" to describe the distinct interaction unit: a double-stranded DNA and a functional protein entity one protein chain or interacting chains bound to the DNA.
A sample PDAgram for 1A A dot. An uppercase-case letter in a DNA sequence represents the base is in contact with the protein while a lower-case letter is not. Each protein-DNA complex structure is assigned with one of four functional classes "gene regulation", "transferase", "hydrolase" and "others" based on the keywords in the PDB file of a protein-DNA complex structure. Entries with "transcription" or "gene regulation" as keywords belong to the gene regulation class.
The transferase class contains structures with keywords "transferase" or "polymerase" while the hydrolase class consists of PDB entries with annotated function of "hydrolase" or "nuclease". The protein-DNA complex structures that cannot be assigned with any of these three classes are grouped into the "others" category. In case of conflicts, the function of the complex structure is further examined by manual inspection.
For example, a few PDB entries have keywords for both the transferase class and the gene regulation class. All of them were classified as transferase after manual inspection. Sequence comparison is a convenient way for determining the similarity of two macromolecules such as two protein or two DNA sequences.
It would be useful if such sequence comparison could also be done for protein-DNA complexes. Previous studies only compare protein sequences for dataset construction. Since a protein-DNA complex can have multiple protein chains as well as multiple double-stranded DNAs, we take an approach of all-against-all comparison protein vs. DNA of two complexes and report the lower and upper bounds of the sequence identities for protein and DNA separately.
While the sequences of the entire protein chains are used for protein comparison, the DNA sequences used for comparison are not straightforward.
Some protein complexes have long DNA sequences but only a small portion of the sequences are involved in protein-DNA interaction. On the other hand, in some protein-DNA complexes, a large percentage of DNA participates in the binding and interaction with proteins even though the DNA sequences are short.
To address this issue, we first extract the DNA subsequences that interact with proteins since in general the DNA binding motifs are better conserved while the flanking sequences showed less conservation. The protein-binding DNA fragment is defined as the longest DNA subsequence bounded by two bases that are in contact with the protein plus one flanking base on each side 5' and 3'.
Within the subsequence, at most three consecutive bases are allowed to be not in contact with the protein. If there is no base-protein contact in a double-stranded DNA, the double-stranded DNA is excluded from sequence comparison. Likewise, protein chains that are not in contact with any bases of DNAs are also excluded from sequence comparison.
ALIGN [ 26 , 27 ] is used for protein sequence comparison, with gap opening and extension penalty of and -2, respectively. As for the DNA sequence comparison, we used an in-house program to perform gapless alignments since the binding motifs are generally short. Sequence identity is defined as the number of identical residues or bases in the alignment divided by the length of the shorter sequence.
To test the efficiency of PDA that uses only two distances H-distance and stagger distance for base-pair detection, we compared the performance of PDA with 3DNA [ 13 ], a program widely-used for DNA structure analysis, on a dataset of protein-DNA complex structures that are solved by X-ray crystallography with high resolution less than 3.
Each cell has a value of 1 if two bases form a pair and 0 otherwise. Through manual inspection, we found that many of these "false positive" base-pairs are possibly true base-pairs.
Our simple but effective approach uses less than five distance calculations per base-pair while 3DNA employs a least square fitting procedure to obtain a reference frame for each base followed by comparing six geometrical parameters from two reference frames for a pair of bases.
Most of the PDA output is self-explanatory. Several notable features of PDA are as follows. However, in the original literature for 1ZX4 [ 31 ], three copies of the double-stranded DNA were shown to bind to the same protein dimer on two different DNA binding domains.
We found that about Major groove contact ratio in a non-redundant dataset of protein-DNA complex structures. To further demonstrate PDA's utility in studying systems biology and structure-based transcription factor binding site prediction, we generated a non-redundant dataset with protein-DNA complex structures that are involved in gene regulation.
First, a total of protein-DNA complex structures that were solved using X-ray crystallography with resolutions less than 3. Application of the above procedure resulted in complex structures. The length of most of the DNA sequences ranges from 6 to 18 base pairs. The complex structures with DNA shorter than 6 bps and longer than 18 bps were removed and a set of Set complex structures were generated for further studies.
DNA sequence length and similarity analysis in Set In general there is a trade-off between "redundancy" and "dataset size" for statistical analysis when constructing a dataset especially if the data available is not large enough as in the case of protein-DNA complex structures.
For example, when only protein sequences are used for protein-DNA complex comparison, a low sequence identity cutoff e.
This dataset offers low-redundancy but lacks power in statistical analysis [ 5 ]. Most PDAs have power management systems in place to extend the battery life. Even if the batteries are so low that you can no longer turn the machine on it will give you plenty of warning before this happens , there's usually enough power to keep the RAM refreshed. If the batteries do run completely out of juice or if you remove them, most devices have an internal backup battery that provides short-term power typically 30 minutes or less until you install a replacement.
This makes backing up or synchronizing your PDA extremely important. In addition to battery power, many PDAs come with AC adapters to run off household electric currents.
A car adapter is also generally available as an accessory. Unlike the LCD screens for desktop or laptop computers, which are used solely as output devices, PDAs use their screens for output and input. Almost all PDAs now offer color displays. PDAs vary in how you input data and commands. Some devices use a stylus and touch screen exclusively in combination with a handwriting recognition program. Using a plastic stylus, you draw characters on the device's display or dedicated writing area. Software inside the PDA converts the characters to letters and numbers.
On Palm devices, the software that recognizes these letters is called Graffiti. Graffiti requires that each letter be recorded in a certain way, and you must use a specialized alphabet. For example, to write the letter "A," you draw an upside-down V. The letter "F" looks like an inverted L. To help Graffiti make more accurate guesses, you must draw letters on one part of the screen and numbers in another part.
Letter Recognizer and Block Recognizer are similar to Graffiti and require specialized alphabets. By contrast, Transcriber recognizes your "regular" handwriting, as long as you write legibly. It is similar to the handwriting recognition capabilities found on Tablet PCs. If you can't get the hang of PDA handwriting, you can use a miniature onscreen keyboard. It looks just like a regular keyboard, except you tap on the letters with the stylus. Some of these require you to use your thumbs to type.
Each model also has a few buttons and navigation dials to bring up applications and scroll through files. If you're in the market for a PDA, the main question you should consider is, "What will I be using this for most of the time? On the other hand, if you travel frequently and want to stay in touch via e-mail, you need Wi-Fi capability or a smartphone with cellular data service.
Look for a device that easily synchronizes with the PIM software you use on your computer. For example, if you have a Macintosh computer or you don't use Microsoft Outlook, a Palm OS device may be more to your liking.
The device's data entry method is another important consideration. If you plan to use your PDA for e-mail or other text-heavy applications, consider a built-in keyboard. If you can, try out the keyboard before you buy. The size and shape of the device and its display are also important considerations. The device should be comfortable to hold. The display size and clarity should also meet your expectations.
As with the keyboard, it's best to make a trip to a store that sells the devices you're interested in so you can try it out before you buy. If you are interested in a multipurpose device that combines features such as GPS , an MP3 player , or digital camera , look for a device that has these features integrated.
If you plan to use numerous applications or store large files, look for a device that accepts flash memory media cards. Accessories to consider include an additional battery, a car or travel charger, headphones, a carrying case, a plastic screen protector and add-on keyboards.
If you're interested in a smartphone, many of the considerations for purchasing a cell phone apply. Some of the most important things to check include service providers' coverage area, the additional cost for cellular data service if any , and the length of the service contract. Traditional PDAs appear to be less popular than they have been in the past. The emergence and gaining popularity of smart phones and devices that combine other features such as wireless Internet, GPS and multimedia capabilities seem to back this trend.
PDAs are designed to work with desktops or laptops and to make the information in your bigger computers portable. So you need to keep the information up-to-date. PDAs have features that make this easier for you. Each operating system has its advantages. The Palm OS is the market leader, so there is a lot of software written and being developed for it.
But developers are working on software for the PocketPC systems, too. Palm OS takes up less memory and runs faster, and users say it is easier to use. PocketPC takes up more memory and is slower, and users say it is more complicated.
If you keep your PDA data synchronized with your desktop computer, you'll always have a back-up copy. So if you lose your PDA, you'll still have the data. You can also do several things to lock up your PDA's information. In most models, you can use password protection. There are security programs available, too, that can keep someone from getting to your data.
And some applications provide encryption. One thing that PDA makers have done to make their devices work better for Internet access is a process called Web Clipping. Instead of downloading whole Web pages, Web Clipping slices out bits of text information and sends it through the airwaves to your PDA.
News headlines, phone numbers, e-mail and other information can be transmitted this way. Viruses have infected some PDA models. The Phage virus, for example, overwrites some of Palm's executable files. Several companies have devised anti-virus software for PDAs. If you download programs from the Internet, you can be vulnerable to viruses. You have to watch out for the same things that you would if you downloaded a file to your desktop computer.
Published on Jan 6, First a little refresher: Let's go back to what is an account, accounts are basically a place to store data.
We can use the analogy of a vault. The blockchain is the world's bank and that bank can store vaults accounts. Let's put it in more concrete way in web2, as a backend developer you would usually store your data in a file in the server disk or a database, it all goes well because you actually own the server. But in web3 the server belongs to everyone! That is why the next time you talk to the world's bank blockchain you need to tell it:. Public Key In the same way that a Linux user uses a path to look up a file, in Solana we use an address to look up an account.
The address is usually:. Account's data can only be modified by the account's Owner program, If an account is not owned by a program, the program is only permitted to read its data and credit the account.
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