Analysis of structures of known TFs bound to DNA has revealed three different mechanisms of recognition of the specifically bound sequences: (1) the ‘direct readout’ mechanism involving the formation of specific hydrogen bonds and hydrophobic interactions between DNA bases and protein amino acids ( Aggarwal et al., 1988 Anderson et al., 1987 Wolberger et al., 1988) (2) ‘indirect readout’ of the DNA shape and electrostatic potential ( Dror et al., 2014 Hizver et al., 2001 Joshi et al., 2007 Lavery, 2005 Rohs et al., 2005) by protein contacts to the DNA backbone or the minor groove, and (3) water mediated interactions between bases and amino-acids ( Bastidas and Showalter, 2013 Garner and Rau, 1995 Ladbury et al., 1994 Morton and Ladbury, 1996 Patikoglou and Burley, 1997 Poon, 2012 Spolar and Record, 1994).
The binding of transcription factors (TFs) to their specific sites on genomic DNA is a key event regulating cellular processes. In addition, these findings may one day help scientists to predict how strongly two molecules will interact simply by knowing the structures of the molecules involved. It is possible that these mechanisms could also apply to many other molecules that interact with each other through water-molecule bridges.Ī better knowledge of the chemical bonds between transcription factors and DNA bases may in future help efforts to develop new treatments that depend on molecules being able to bind to other molecules. The other DNA sequence was bound equally strongly but through moving water molecules, because this increased the entropy of the system. For one DNA sequence, an enthalpy-based mechanism essentially ‘froze’ the transcription factor to the DNA through rigid water bridges. The results showed that the transcription factors bound to both DNA sequences with similar strength, but via different mechanisms. studied four different human transcription factors that can each bind to two distinct DNA sequences. Most transcription factors can only bind to DNA sequences that are very similar to each other, but some transcription factors can recognize several different kinds of sequences, and until now it was not clear how they could do this. A water molecule that bridges a DNA base with an amino-acid of a protein contributes to enthalpy, but results in loss of entropy, because the system becomes more ordered since the water molecule can no longer move freely.
#Enthalpy vs entropy free#
Entropy measures the disorder of the system – the more disordered the solvent and protein-DNA complex are compared to solvent-containing free DNA and protein, the stronger the binding. Enthalpy relates to how strong the chemical bonds that form between the transcription factors and the DNA bases are, compared to a situation where the transcription factor and DNA do not form a complex and bind to water molecules around them. Two physical concepts known as enthalpy and entropy determine the strength of the connection. Transcription factors glide along DNA and bind to short DNA sequences by attaching to the DNA bases directly or through bridges made up of water molecules. Almost all cells carry the same genetic information, but proteins called transcription factors can regulate the activity of genes so that only a relevant subset of genes is switched on at a particular time. Many organisms – including humans – are built of many different types of cells that perform unique roles.
+–+change+in+heat.jpg "enthalpy vs entropy")
The order or sequence of these bases determines the role of a protein.
#Enthalpy vs entropy code#
The information in the DNA is stored as a code consisting of four chemical bases, often referred to simply as “A”, “C”, “G” and “T”. Then look up the ∆S values of the reactants SO 2 (g) and O 2 (g) and plug it into the equation.Genes are sections of DNA that carry the instructions needed to build other molecules including all the proteins that the cell needs to fulfill its role. If there is a coefficient in front of the substance then you must multiply the substance’s value of ∆S with the coefficient. Plug the value into the equation such that: Look up the value of ∆S of SO 3 (g), the product, on the chart. Classify them either as the reactant(s) or product(s).Ģ(∆S value SO 3 (g)) –
Write out the equation with the substances in them. These values are then put into the equation: If these values are not known, then you can use the ∆S values of the substances in the chemical reaction usually given to you in a chart. Which can be manipulated into ∆S= ∆H-∆G/T One way is by using the known values of ∆H, ∆G, and the temperature of the system and plugging these values in the equation: There are several ways to calculate entropy.
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