In the later stages of drug design projects, accurately predicting relative binding affinities of chemically similar compounds to a biomolecular target is of utmost importance for making decisions based on the ranking of such compounds. So far, the extensive application of binding free energy approaches has been hampered by the complex and time-consuming setup of such calculations. We introduce...

In plants, microRNA (miRNA)-target complementarity has long been considered the predominant factor determining the silencing outcome of the miRNA-target interaction, although the efficacy of such interactions have rarely been appraised in plants. Here, we perform in planta silencing efficacy assays on seven Arabidopsis MYB genes, all of which contain conserved miR159-binding sites of analogous ...

p53, a tumor suppressor protein, has been proven to regulate the cell cycle, apoptosis, and DNA repair to prevent malignant transformation. MDM2 regulates activity of p53 and inhibits its binding to DNA. In the present study, we elucidated the MDM2 inhibition potential of polyphenols (Apigenin, Fisetin, Galangin and Luteolin) by MD simulation and MM/PBSA free energy calculations. All polyphenol...

We develop a theoretical framework on the mechanism of combinatorial binding of transcription factors (TFs) with their specific binding sites on DNA. We consider three possible mechanisms viz. monomer, hetero-oligomer and coordinated recruitment pathways. In the monomer pathway, combinatorial TFs search for their targets in an independent manner and the protein-protein interactions among them w...

A coherent framework is presented for determining the free energy change accompanying ligand binding to protein receptors. The most important new feature of the method is the contribution of the flexibility of the free ligand, and hence its conformational change on binding, to the free energy. Flexibility introduces two additional terms in the free energy difference: the internal energy differe...

the acidity constants (pka) of thirty four (34) ;-substituted carboxylic acids in aqueous solution havebeen calculated using conductor-like polarizable continuum (c-pcm) solvation model. the gasphaseenergies at the density functional theory (dft-mpw1pw91) and solvation energies athartree fock (hf) are combined to estimate the pka values which are very close to the experimentalvalues where, and ...