S. Sundar Raman

Exploring the changes in the structure of α-helical peptides adsorbed onto a single walled carbon nanotube using classical molecular dynamics simulation.

Classical molecular dynamics (MD) simulation has been carried out in an explicit solvent environment to understand the interaction between the single walled carbon nanotube (SWCNT) and α-helix. A polyalanine peptide consisting of 40 alanine residues has been chosen as the model for the α-helix (PA(40)). Results reveal that the SWCNT induces conformational changes in PA(40). Furthermore, breakage of hydrogen bonds in the chosen model peptides has been observed, which leads to conformational transitions (α → turns) in different parts of the PA(40). Owing to these transitions, regions of different structural and energetic stability are generated in PA(40) which enable the PA(40) to curl around the surface of the SWCNT. The overall observations obtained from the MD simulations are not significantly influenced by the starting geometry and the choice of the force field. Although the qualities of structural information obtained from the MD simulation using ff03 and OPLS are different, the overall observation derived from the ff03 is similar to that of OPLS. Results from the MD simulation on the interaction of the α-helical fragment of the SNARES protein with the SWCNT elicit that the amino acid composition influences the interaction pattern. The wrapping of the α-helical fragment of the SNARES onto the SWCNT is similar to that of PA(40). Overall, there is a considerable decrease in the helical content of peptides upon interaction with SWCNTs, in agreement with the experimental findings.

Studies on the structure and stability of cyclic peptide based nanotubes using oligomeric approach: a computational chemistry investigation.

In this study, an attempt has been made to investigate the structure, dynamics, and stability of cyclic peptide nanotubes (CPNTs) formed by the self-assembly of cyclic peptides (CPs) using classical molecular dynamics (MD) simulation and semiempirical quantum chemistry calculation employing PM6 Hamiltonian with the dispersion correction and hydrogen-bonding interaction (DH2). The structure and energetics of monomer and various oligomeric CPNTs have been investigated by considering the (cyclo-[(D-Ala-L-Ala)(4)]) peptide as the model for CP. Although the formation of CPNTs has been intensively studied, the present study adds valuable information to the de novo design of CPNTs. Various geometrical parameters extracted from the MD simulation reveal that the terminal residues are loosely hydrogen bonded to the inner subunits regardless of degree of oligomerization. The hydrogen bonds present in the inner core regions are stronger than the terminal residues. As the degree of oligomerization increases, the stability of the tube increases due to the hydrogen-bonding and stacking interactions between the subunits. The results show that the binding free energy increases with the extent of oligomerization and reaches saturation beyond pentamer CPNT. In addition, hydrophobic and electrostatic interactions play crucial roles in the formation of CPNTs. Analysis of both structure and energetics of the formation of CPNTs unveils that the self-assembly of dimer, trimer, and tetramer CPNTs are the essential steps in the growth of CPNTs.

Molecular Dynamics Investigations on the Effect of D Amino Acid Substitution in a Triple-Helix Structure and the Stability of Collagen

Studies on the structure and stability of peptides and proteins during l-->d configurational change are certainly important for the designing of peptides with new biological activity and protein engineering. The l-->d amino acid (d AA) changes have been observed in aged proteins such as collagen. Hence, in this study, an attempt has been made to explore the effect of the replacement of l amino acid (l AA) in the model collagen-like peptides with d AA and the origin of structural stability (destability) has been traced using the molecular dynamics (MD) method employing the AMBER force field. Our results reveal that the substitution of d AA produces a large local disruption to the triple-helical structure. Formation of a kink (bulge) at the site of substitution is observed from the detailed analysis of MD trajectory. However, this local perturbation of kinked helix changes the direction of the helices and affects the relative orientation of the respective AA residues for helix-helix interaction, enough to affect the overall stability of the model collagen-like peptide. The destabilization energy per d Ala substitution is 7.87 kcal/mol, which is similar to the value for the Gly-->Ala mutation in collagen. Since the Gly-->Ala mutation is involved in genetic disorders such as osteogenesis imperfecta (OI), the l-->d configurational change may produce a similar effect on collagen.

Role of Length-Dependent Stability of Collagen-like Peptides

Understanding the structure, folding, and stability of collagen is complex because of its length and variations in the amino acid (AA) sequence composition. It is well known that the basic constituent of the collagen helix is the triplet repeating sequence of the form Gly-X(AA)-Y(AA). On the basis of previous models and with the frequency of occurrence of the triplets, the ((Gly-Pro-Hyp)n)3 (where n is the number of triplets) sequence replicate has been chosen as the model for the most stable form of the collagen-like sequence. With a view to understand the role of sequence length (or the number of triplets) on the stability of collagen, molecular dynamics simulations have been carried out by varying the number of triplet units on the model collagen-like peptides. The results reveal that five triplets are required to form the stable triple helix. Further analysis shows that the intermolecular structural rigidity of the imino acid residues, hydrogen bonding, and water structure around the three chains of the triple helix play the dominant roles on its structure, folding, and stabilization.

Structural Basis for the Varying Propensities of Different Amino Acids To Adopt the Collagen Conformation

Although previous experimental studies have shown the positional preference of different amino acids (AAs) to form a stable triple helical collagen motif, the structural basis for the variations in the sequence and the positional propensity has not been systematically investigated. Thus, we have here probed the origin of the structural stability offered by the 20 naturally occurring AAs to collagen by means of classical molecular dynamics (MD) simulation. Simulations were carried out on 39 collagen-like peptides employing a host-guest approach. The results show that the propensity of the different AAs to adopt collagen-like conformations depends primarily on their ϕ and ψ angle preferences. Changes in these angles upon substitution of different AAs in the X(AA) and Y(AA) positions in the canonical ((Gly-X(AA)-Y(AA))(7))(3) motif dictate the formation of interchain hydrogen bonds, solvent interactions, and puckering of neighboring imino acids and, thus, the structural stability of the collagen. The role of solvent-mediated hydrogen bonds in the stabilization of collagen has also been elucidated from the MD simulations. In addition to the conventional hydrogen bonds known to be present in collagen, a hitherto unidentified direct interchain hydrogen bond, between the X(AA) N-H group and the Hyp O-H group of the neighboring chain, was observed during the simulations. Its occupancy was ∼36% when Leu was present at the X(AA) position.

Helix Forming Tendency of Valine Substituted Poly-Alanine: A Molecular Dynamics Investigation

In this study, classical molecular dynamics simulations have been carried out on the valine (guest) substituted poly alanine (host) using the host-guest peptide approach to understand the role of valine in the formation and stabilization of helix. Valine has been substituted in the host peptide starting from N terminal to C terminal. Various structural parameters have been obtained from the molecular dynamics simulation to understand the tolerance of helical motif to valine. Depending on the position of valine in the host peptide, it stabilizes (or destabilizes) the formation of the helical structure. The substitution of valine in the poly alanine at some positions has no effect on the helix formation (deformation). It is interesting to observe the coexistence of 3 10 and alpha-helix in the peptides due to the dynamical nature of the hydrogen bonding interaction and sterical interactions.