Drug like methotrexate were used in the present study because of dual impor-tance, both for clinicians as well as an interest of basic scientists. Methotrexate, an antineoplastic agent is used for malignant as well as non malignant conditions and become teratogenic & mutagenic in nature. They prevent cell proliferation by incorporated into DNA during the "S"- phase of the cell- cycle and inhibit rapidly dividing normal somatic cell-division including germ cells because of an-tagonist of folic acid synthesis by inhibiting dihydrofolate reductase an essential enzyme required for the conversion of folic acid to tetrahydrofolic acid. The ra-tional behind this study is to observe binding sites activity of native methotrexate structure to DNA, and dihydrofolate reductase (protein) as well as mutated structure of drug (methotrexate) using different software of structural modeling. For drug (methotrexate) - protein structure interaction, homology modeling, also known as comparative modeling, was used in the present study for con-structing model of a protein from its amino acid sequence to enhance activity of the drug by structural modification. All homology modeling techniques help for the identification of one or more known protein structures (known as "tem-plates" or "parent structures") resemble to the structure of query sequence, and on the production of an alignment, which maps residues in the query sequence. The sequence alignment and template structure are then used to produce a structural model of the target site of drug or protein. Interestingly in the present study indicates the significant interaction between the drug and DNA/ proteins were noticed which could be further useful in reaching qualitative and quantita-tive conclusions about the query sequence of developing new molecule (drug ac-tion), especially in formulating hypotheses about why certain residues are con-served and making toxic side effects which may in turn lead to experiments to test hypotheses of drug mediated toxicity.
Ajit. K Saxena, Divya Singh, Gajendra Singh