Chemgenome is based on the hypothesis that both the structure of the DNA and its interactions with regulatory proteins and polymerases decide the function of a DNA sequence. It uses a simple three-parameter model based on Watson- Crick hydrogen-bonding energy, base-pair stacking energy, and a third parameter which is related to Protein-Nucleic Acid interactions. Each of these parameters acts as a dimension for a three-dimensional unit vector, whose orientation differs for each trinucleotide.
DNA sequence is made up of set of four bases (A, T, G, C) which combine in different possible manner to give 64 unique codons. Each of the 64 codons(trinucleotides) are assigned a X(Hydrogen Bonding Energy), Y(Stacking Energy) and Z(protein-Nucleic acid interaction).

The first component was constructed by finding the Hydrogen bonding energy of trinucleotides(codons).
■ The second component was constructed by finding the Stacking energy(sum of electrostatic, hydrophobic and other forces which the trinucleotides are exposed to when it is stacked with other nucleotides in the B-DNA form).
■ The third component of the vector reflects the DNA protein interactions. It's assignment follows the “Conjugate” rule which is derived from the Wobble Hypothesis (For more on conjugate rule, refer to [Jayaram, B. Beyond the wobble: the rule of conjugates. J. Mol. Evol. 1997, 45, 704-705].

Every sequence is broken down into trinucleotides, the three components for each trinucleotide are added up. The values assigned to all the trinucleotides are normalized to lie in the range [-1,1]. These unit vectors are then plotted on unit spheres.
A physical separation of the vectors corresponding to coding DNA sequences and the non-coding DNA sequences was observed by plotting them as dots on a 3D plane. All the coding DNA sequences are represented as blue dots while the non-coding DNA sequences are represented as red dots.

Once we get this line, all we have to do is convert a new DNA sequence into a point and then check on which side of the line it lies. If it lies on the side with the red points, then it is a gene else it is a non-gene.

This physical separation of the vectors corresponding to genes and non-genes is the basis of the physico-chemical model of Gene Evaluation. Once the best separating plane is obtained, we only need to check if the new DNA sequence lies on the Gene side of the plane or the other side.
Physico-chemical evaluation has proven accurate for Prokaryotes to an accuracy of >95% and forms the basis of Chemgenome 1.1.

Chemgenome 2.0 goes a step further and predicts the coding regions in Prokaryotes if a whole genome or part of genome is given as an input.
To know more about this physico-chemical model, refer to

Chemgenome 2.0 goes a step further and predicts the coding regions in Prokaryotes if a whole genome or part of genome is given as an input.

To know more about this physico-chemical model, refer to

[1] Progenie "Decoding the Design Principles of Amino Acids and the Chemical Logic of Protein Sequences", Jayaram, B. Available from Nature Precedings. http://hdl.handle.net/10101/npre.2008.2135.1 2008 [Read Paper]

[2]"Prokaryotic Gene Finding based on Physicochemical Characteristics of Codons Calculated from Molecular Dynamics Simulations", Singhal P, Jayaram B, Dixit S B and Beveridge D L, Biophys. J. ,2008, 94(11), 4173-4183. [ Read Paper ]

[3] "A Physico-Chemical model for analyzing DNA sequences", Dutta S, Singhal P, Agrawal P, Tomer R, Kritee, Khurana E and Jayaram B, J.Chem. Inf. Mod., 2006, 46(1), 78-85.[ ABSTRACT ].

[4] "Beyond the Wobble : The rule of conjugates", Jayaram B, Journal of Mol. Evol., 1997,45,704-705.