Structural and dynamical aspect of DNA motif sequence specific binding of AP-1 transcription factor.

Activator protein-1 (AP-1) comprises one of the largest and most evolutionary conserved families of ubiquitous eukaryotic transcription factors that act as a pioneer factor. Diversity in DNA binding interaction of AP-1 through a conserved basic-zipper (bZIP) domain directs in-depth understanding of how AP-1 achieves its DNA binding selectivity and consequently gene regulation specificity. Here, we address the structural and dynamical aspects of the DNA target recognition process of AP-1 using microsecond-long atomistic simulations based on the structure of the human AP-1 FosB/JunD bZIP-DNA complex.

Sequence-Specific Structural Features and Solvation Properties of Transcription Factor Binding DNA Motifs: Insights from Molecular Dynamics Simulation.

Sequence-specific recognition of transcription factor (TF) binding motifs in the target site of DNA over the vast amount of non-target DNA is of primary importance for the transcriptional regulation of gene expression by the TFs. Binding of TFs to the target site of DNA relies not only on the direct contact formation but also on the structural and conformational features of DNA. Recognition of DNA structural features or shape readout by proteins is an important factor in the context of TF-DNA interaction.

Multi-scale gene regulation mechanism: Spatiotemporal transmission of genetic information.

Gene expression is regulated by many factors, including transcription factors, chromatin three-dimensional topology, modifications of DNA and histone proteins, and non-coding RNAs. The execution of these complex mechanisms requires an effectively coordinated regulation system. In this review, we emphasize that the multi-scale heterogeneous DNA sequence plays a fundamental and important role for gene expression activity and usage of different means of epigenetic regulation.

Effect of biphosphate salt on dipalmitoylphosphatidylcholine bilayer deformation by Tat polypeptide.

Translocation of positively charged cell penetrating peptides (CPP) through cell membrane is important in drug delivery. Here we report all-atom molecular dynamics simulations to investigate how a biphosphate salt in a solvent affects the interaction of a CPP, HIV-1 Tat peptide with model dipalmitoylphosphatidylcholine (DPPC) lipid bilayer. Tat peptide has a large number of basic arginines and a couple of polar glutamines.

A perspective on the molecular simulation of DNA from structural and functional aspects.

As genetic material, DNA not only carries genetic information by sequence, but also affects biological functions ranging from base modification to replication, transcription and gene regulation through its structural and dynamic properties and variations. The motion and structural properties of DNA involved in related biological processes are also multi-scale, ranging from single base flipping to local DNA deformation, TF binding, G-quadruplex and i-motif formation, TAD establishment, compartmentalization and even chromosome territory formation, just to name a few. The sequence-dependent physical properties of DNA play vital role in all these events, and thus it is interesting to examine how simple sequence information affects DNA and the formation of the chromatin structure in these different hierarchical orders.

Self-assembly in amphiphilic macromolecules with solvent exposed hydrophobic moieties.

Self-assembly by amphiphilic molecules with solvent exposed hydrophobic groups are relevant in biomolecular systems as well as in technological applications. Here we study such self-assembly in these systems using a model system of spherical particles having charge at core but solvent repelling surface, using Monte-Carlo simulations and mean field treatment. We find that solvophobicity mediated attraction leads aggregation, while electrostatic repulsions control stability of finite clusters.

Quantum chemical studies on anion specificity of CNN motif in functional proteins.

Anion binding CNN motif is found in functionally important regions of protein structures. This motif based only on backbone atoms from three adjacent residues, recognizes free sulphate or phosphate ion as well as phosphate groups in nucleotides and in a variety of cofactors. The mode of anion recognition and microscopic picture of binding interaction remains unclear.

Anion induced conformational preference of C NN motif residues in functional proteins.

Among different ligand binding motifs, anion binding C NN motif consisting of peptide backbone atoms of three consecutive residues are observed to be important for recognition of free anions, like sulphate or biphosphate and participate in different key functions. Here we study the interaction of sulphate and biphosphate with C NN motif present in different proteins. Instead of total protein, a peptide fragment has been studied keeping C NN motif flanked in between other residues.

Computational Framework for Prediction of Peptide Sequences That May Mediate Multiple Protein Interactions in Cancer-Associated Hub Proteins.

A considerable proportion of protein-protein interactions (PPIs) in the cell are estimated to be mediated by very short peptide segments that approximately conform to specific sequence patterns known as linear motifs (LMs), often present in the disordered regions in the eukaryotic proteins. These peptides have been found to interact with low affinity and are able bind to multiple interactors, thus playing an important role in the PPI networks involving date hubs. In this work, PPI data and de novo motif identification based method (MEME) were used to identify such peptides in three cancer-associated hub proteins-MYC, APC and MDM2.