PubMed Health⌕ Search

Biomedical subjects

D Faulhammer

Publications and source records attributed to D Faulhammer.

5 recordsLinked to original sources

Molecular computation: RNA solutions to chess problems.

We have expanded the field of "DNA computers" to RNA and present a general approach for the solution of satisfiability problems. As an example, we consider a variant of the "Knight problem," which asks generally what configurations of knights can one place on an n x n chess board such that no knight is attacking any other knight on the board. Using specific ribonuclease digestion to manipulate strands of a 10-bit binary RNA library, we developed a molecular algorithm and applied it to a 3 x 3 chessboard as a 9-bit instance of this problem. Here, the nine spaces on the board correspond to nine "bits" or placeholders in a combinatorial RNA library. We recovered a set of "winning" molecules that describe solutions to this problem.

Algorithms↗

Fidelity of enzymatic ligation for DNA computing.

We describe a convenient assay for rapid qualitative evaluation of hybridization/ligation fidelity. The approach uses randomized probe strands of DNA and restriction enzyme digestion after amplification of reaction products by the polymerase chain reaction (PCR). We report ligation efficiencies and fidelities of two DNA ligases, T4 DNA ligase and Thermus aquaticus (Taq) DNA ligase, over a range of temperatures.

DNA↗

Chess games: a model for RNA based computation.

Here we develop the theory of RNA computing and a method for solving the 'knight problem' as an instance of a satisfiability (SAT) problem. Using only biological molecules and enzymes as tools, we developed an algorithm for solving the knight problem (3 x 3 chess board) using a 10-bit combinatorial pool and sequential RNase H digestions. The results of preliminary experiments presented here reveal that the protocol recovers far more correct solutions than expected at random, but the persistence of errors still presents the greatest challenge.

Animals↗

Counting DNA: estimating the complexity of a test tube of DNA.

We consider the problem of estimation of the 'complexity' of a test tube of DNA. The complexity of a test tube is the number of different kinds of strands of DNA in the test tube. It is quite easy to estimate the number of total strands in a test tube, especially if the strands are all the same length. Estimation of the complexity is much less clear. We propose a simple kind of DNA computation that can estimate the complexity.

Animals↗

Characterization and divalent metal-ion dependence of in vitro selected deoxyribozymes which cleave DNA/RNA chimeric oligonucleotides.

By in vitro selection, a variety of catalytic DNA oligonucleotides were obtained which cleave chimeric oligonucleotides at a single ribonucleotide position embedded within a deoxyribonucleotide context in the presence or absence of divalent metal ions. After several cycles of selection/amplification in the absence and in the presence of low amounts of Mg2+ two different types of catalysts emerged: one type depended strongly on Mg2+ or other divalent metal ions, the other type performed cleavage reactions independently of Mg2+ in the presence of spermine. Experimental analysis of the secondary structure of some of the selected deoxyribozymes was carried out by chemical probing. The ribonucleotide in the selected catalysts is unpaired and presents the cleavage site to the attacking nucleophile. Our results suggest that the main selection criterion under metal-free conditions was a favourable arrangement of the attacking nucleophile and the phosphate leaving group. The cleavage rates of the selected divalent metal independent catalysts are within the same order of magnitude as the rate of metal independent substrate hydrolysis in the hammerhead ribozyme. One of the metal dependent catalysts showed an unexpected preference for Ca2+ instead of Mg2+. In this deoxyribozyme binding of Ca2+ occurred co-operatively whereas binding of Mg2+ did not. Comparison of the secondary structure and reactivity of this catalyst with Mg2+ and Ca2+ suggests that here a special binding pocket for Ca2+ was selected. This deoxyribozyme achieved a rate acceleration of substrate cleavage in the order of at least 10(4) compared to the uncatalysed reaction performing a cleavage mechanism similar to that of the hammerhead or hairpin ribozyme.

Allosteric Regulation↗