Efficient prediction of protein conformational pathways based on the hybrid elastic network model.

Various computational models have gained immense attention by analyzing the dynamic characteristics of proteins. Several models have achieved recognition by fulfilling either theoretical or experimental predictions. Nonetheless, each method possesses limitations, mostly in computational outlay and physical reality. These limitations remind us that a new model or paradigm should advance theoretical principles to elucidate more precisely the biological functions of a protein and should increase computational efficiency. With these critical caveats, we have developed a new computational tool that satisfies both physical reality and computational efficiency. In the proposed hybrid elastic network model (HENM), a protein structure is represented as a mixture of rigid clusters and point masses that are connected with linear springs. Harmonic analyses based on the HENM have been performed to generate normal modes and conformational pathways. The results of the hybrid normal mode analyses give new physical insight to the 70S ribosome. The feasibility of the conformational pathways of hybrid elastic network interpolation (HENI) was quantitatively evaluated by comparing three different overlap values proposed in this paper. A remarkable observation is that the obtained mode shapes and conformational pathways are consistent with each other. Our timing results show that HENM has some advantage in computational efficiency over a coarse-grained model, especially for large proteins, even though it takes longer to construct the HENM. Consequently, the proposed HENM will be one of the best alternatives to the conventional coarse-grained ENMs and all-atom based methods (such as molecular dynamics) without loss of physical reality.

A mass weighted chemical elastic network model elucidates closed form domain motions in proteins.

An elastic network model (ENM), usually Cα coarse-grained one, has been widely used to study protein dynamics as an alternative to classical molecular dynamics simulation. This simple approach dramatically saves the computational cost, but sometimes fails to describe a feasible conformational change due to unrealistically excessive spring connections. To overcome this limitation, we propose a mass-weighted chemical elastic network model (MWCENM) in which the total mass of each residue is assumed to be concentrated on the representative alpha carbon atom and various stiffness values are precisely assigned according to the types of chemical interactions. We test MWCENM on several well-known proteins of which both closed and open conformations are available as well as three α-helix rich proteins. Their normal mode analysis reveals that MWCENM not only generates more plausible conformational changes, especially for closed forms of proteins, but also preserves protein secondary structures thus distinguishing MWCENM from traditional ENMs. In addition, MWCENM also reduces computational burden by using a more sparse stiffness matrix.

DNA nanotube formation based on normal mode analysis.

Ever since its inception, a popular DNA motif called the cross tile has been recognized to self-assemble into addressable 2D templates consisting of periodic square cavities. Although this may be conceptually correct, in reality certain types of cross tiles can only form planar lattices if adjacent tiles are designed to bind in a corrugated manner, in the absence of which they roll up to form 3D nanotube structures. Here we present a theoretical study on why uncorrugated cross tiles self-assemble into counterintuitive 3D nanotube structures and not planar 2D lattices. Coarse-grained normal mode analysis of single and multiple cross tiles within the elastic network model was carried out to expound the vibration modes of the systems. While both single and multiple cross tile simulations produce results conducive to tube formations, the dominant modes of a unit of four cross tiles (one square cavity), termed a quadruplet, fully reflect the symmetries of the actual nanotubes found in experiments and firmly endorse circularization of an array of cross tiles.